Ma telomere komanso kufupika kwake kumayambitsa shuga

Ma Micrograph a ma chromosome a anthu okhala ndi ma telomeres (omwe akuwonetsedwa mwa pinki). (Chithunzi: Mary Armanios)

Ma Telomeres akubwereza mndandanda wa DNA womwe umateteza ku malekezero a ma chromosomes. Thupi likamakula, nthawi zambiri limafupika. Zikatero, maselo amalephera kugawa mwachizolowezi, ndipo pamapeto, amafa. Kufupikitsa kwa Telomere kumalumikizidwa ndi khansa, matenda am'mapapo, ndi matenda ena okalamba. Matenda a shuga, omwe amaphatikizidwanso ndi ukalamba, amakhudza munthu mmodzi mwa akulu anayi woposa zaka 60.

Kafukufuku wa asayansi ku yunivesite ya Johns Hopkins, omwe adasindikizidwa mu magazini ya PloS One, adakhazikika pa zomwe a Mary Armanios, omwe adaganizira za kukhalapo kwa ubale weniweni pakati pa zochitika za matenda ashuga komanso dyskeratosis (dyskeratosis congenital), matenda achilendo obadwa nawo chifukwa chophwanya njira yokonza kutalika kwa telomere. Odwala omwe ali ndi cholowa chokhala ndi dyskeratosis, kusakhazikika kwa msanga ndi kulephera koyambirira kwa ziwalo zambiri nthawi zambiri kumawonedwa.

“Congenital diskeratosis ndi matenda omwe amachititsa kuti anthu azikalamba asanabadwe. Tinkadziwa kuti kuchuluka kwa anthu odwala matenda ashuga kumawonjezeka ndi ukalamba, choncho tidayesetsa kuti pakhale kulumikizananso pakati pa ma telomeres ndi matenda ashuga, "anatero kafukufuku Armanios, pulofesa wothandizira pa onology pa Kimmel Cancer Center, University of Johns Hopkins.

Odwala omwe ali ndi matenda ashuga, osapatsidwa insulin yokwanira, ndipo maselo awo sangathe kuwagwiritsa ntchito moyenera, zomwe zimayambitsa kuphwanya malamulo a shuga.

Armanios adaphunzira mbewa zazifupi ndi ma telomeres achidule komanso maselo ake opanga insulin. Adapeza kuti ngakhale panali ma cell a beta ambiri owoneka bwino, kuchuluka kwa shuga m'magazi amenewa kunali kokulirapo, ndipo maselo amatulutsa insulin iwiri kuposa nyama za gulu lotsogolera.

"Izi zikufanana ndi magawo oyambirira a matenda ashuga mwa anthu, pamene maselo amavutika kutulutsa insulin chifukwa cha shuga," akufotokoza Armanios. "Ndi mbewa zoterezi m'malo ambiri obisika insulin"Kuchokera pakupanga mphamvu pogwiritsa ntchito mitochondria mpaka calcium, maselo amagwira ntchito pang'ono," anatero Armanios.

M'maselo a beta a mbewa zokhala ndi ma telomeres achidule, asayansi apeza kuthekera kwa mtundu wa p16 wogwirizana ndi ukalamba ndi matenda ashuga. Kuphatikiza apo, mitundu yambiri yamayendedwe ofunikira kuti insulin itulutsidwe, kuphatikizapo njira yomwe imayang'anira kuwonetsera kwa calcium, idasinthidwa mwa iwo. Gulu lolamulira, palibe zolakwika zotere zomwe zidapezeka.

Kafukufuku wam'mbuyomu adawonetsa kuti odwala matenda ashuga amatha kukhala ndi ma telomeres achidule, koma kodi amawonjezeka chiwopsezo cha matenda a shuga kapena chotsatira cha matendawa, sichikudziwika bwinobwino.

“Ukalamba ndi chiopsezo chachikulu cha matenda ashuga. Kuphatikiza apo, cholowa m'mabanja chimagwira ntchito yofunika kwambiri. Kutalika kwa ma telomeres ndi gawo lobadwa nawo ndipo kungapangitse anthu kuyamba kukonda matenda ashuga, "akukhulupirira Armanios.

Kutengera ndi ntchitoyi, Armanios akutsimikiza kuti kutalika kwa telomere kumatha kugwira ntchito yopanga chitukuko matenda ashuga. Kafukufuku wowonjezereka, asayansi akukonzekera kuti adziwe ngati zingatheke kuneneratu kuopsa kwa matendawa kutengera kutalika kwa telomere. "

Ma telomere komanso kufupika kwake kumayambitsa shuga

Ma telomere komanso kufupika kwake kumayambitsa shuga

Kodi ndichifukwa chiyani anthu omwe amakhala ndi mafuta ambiri am'mimba amawonjezera kukana kwa insulin komanso kuthekera kwa matenda ashuga? Zakudya zopanda pake, moyo wongokhala ndi kupsinjika kumathandizira kuti pakhale mafuta am'mimba komanso kuwonjezeka kwa shuga m'magazi. Mwa anthu omwe ali ndi m'mimba, ma telomere amakhala amafupikitsa zaka <5>, ndipo zikuwoneka kuti kuchepa kwawo kumakulitsa vutoli chifukwa cha kukana insulini. Pakufufuza kwa ku Denmark komwe mapasa 338 adatenga nawo gawo, zidapezeka kuti ma telomeres achidule ndi omwe amayambitsa kukana insulini pazaka 12 zotsatira. M'mapasa awiri aliwonse, m'modzi mwa iwo omwe ma telomeres awo anali afupifupi adawonetsa kukana kwambiri kwa insulin <6>.

Asayansi awonetsa mobwerezabwereza mgwirizano pakati pa telomeres lalifupi ndi matenda ashuga. Ma telomeres achidule amawonjezera mwayi wokhala ndi matenda ashuga: anthu omwe ali ndi cholowa chaifupi telomere syndrome ali ndi mwayi wokhala ndi matendawa kuposa anthu ena onse. Matenda a shuga amayambira molawirira ndipo amakula mwachangu. Kafukufuku wa amwenye, omwe pazifukwa zingapo ali pachiwopsezo chachikulu cha matenda ashuga, amaperekanso zokhumudwitsa. Ku India wokhala ndi ma telomeres achidule, mwayi wokhala ndi matenda ashuga mzaka zisanu zikubweranso kawiri kuposa nthumwi za mtundu womwewo wokhala ndi ma telomeres <7>. Kuwunika kwa meta komwe kunakhudza anthu opitilira 7,000 kunawonetsa kuti ma telomeres amfupi m'magazi amawu ndi chizindikiro chodalirika cha matenda am'tsogolo a shuga [8].

Sitikudziwa njira yopanga matenda a shuga, komanso titha kuyang'anitsitsa mu kapamba kuti tiwone zomwe zimachitika mmenemo. Mary Armanios ndi anzawo adawonetsa kuti mbewa, ma telomere atachepetsedwa mthupi lonse (asayansi adakwaniritsa izi ndi kusintha kwa majini), maselo a pancreatic beta amataya kutulutsa insulin <9>. Ma cell a stem mu kanyumba akalamba, ma telomeres awo akuchepera kwambiri, ndipo salinso kubwezeretsanso kuchuluka kwa maselo a beta omwe ali ndi udindo wopanga insulin komanso kuwongolera msinkhu wake. Maselo awa amafa. Ndipo ndikulemba kuti matenda ashuga amayamba bizinesi. Ndi mtundu wachiwiri wa matenda ashuga II, maselo a beta samafa, koma magwiridwe akewo ndi operewera. Chifukwa chake, pankhaniyi, nawonso, mawu achidule am'mimba kapamba angatenge gawo.

Mwa munthu wina wathanzi, mlatho kuchokera pamimba kumimba mpaka matenda a shuga ungayikidwe ndi bwenzi lathu lakale - kutupa kosatha. Mafuta am'mimba amathandizira kwambiri kukulitsa kutupa kuposa, titero, mafuta m'chiuno. Maselo amtundu wa Adipose amapanga zinthu zomwe zimapangitsa kuti maselo aziteteza chitetezo chamthupi, zisanafike pang'onopang'ono, zimapangitsa kuti ziwonongeke komanso kuwononga telomeres. Monga momwe mukukumbukira, maselo akale, nawonso, amavomerezedwa kuti atumize zizindikiro zosayimira zomwe zimalimbikitsa kutupa mthupi lonse - bwalo loipa limapezeka.

Ngati muli ndi mafuta ochulukirapo am'mimba, muyenera kusamala kuti mudziteteze ku kutupa kosatha, telomeres yochepa, ndi metabolic syndrome. Koma musanadye chakudya kuti muchotse mafuta am'mimba, werengani chaputala ichi mpaka kumapeto: mutha kusankha kuti kadyedwe kamangokulira. Osadandaula: tikukupatsani njira zinanso zotithandizira kuti kagayidwe kanu kagwire.

Wotsutsa nkhani yasayansi yokhudza zamankhwala ndi chisamaliro chaumoyo, wolemba ntchito yasayansi - Brailova Nataliya Vasilievna, Dudinskaya Ekaterina Nailevna, Tkacheva Olga Nikolaevna, Shestakova Marina Vladimirovna, Strazhesko Irina Dmitrievna, Akasheva Dariga Uaydinichna, Plkhova Ekaterina Verekchina Anatolyevich

Cholinga cha phunziroli chinali kuphunzira za ubale wa kutupa kwakatundu, kupsinjika kwa oxidative, ndi telomere biology mwa anthu omwe ali ndi matenda a shuga 2 a mellitus (T2DM). Zida ndi njira. Phunziroli lidaphatikizapo odwala 50 omwe ali ndi matenda a shuga a 2 popanda mawonekedwe a matenda amtima (CVD) ndi anthu a 139 pagulu lolamulira. Mkhalidwe wa metabolism ya carbohydrate, kuchuluka kwa oxidative nkhawa (MDA malondialdehyde) ndi kutupa kosatha (fibrinogen, protein ya C-reactive CRP, interleukin-6 IL-6) kuyesedwa, kutalika kwa ma lymphocytic telomeres ndi telomerase zochita anayeza. Zotsatira Odwala omwe ali ndi matenda a shuga a mtundu wa 2, kutalika kwa telomere kunali kochepa (p = 0.031), zochitika za telomerase zinali zochepa (p = 0.039), ndipo kuchuluka kwa kutupa (CRP ndi fibrinogen level) kunali kokulirapo kuposa pagulu lolamulira. Odwala onse adagawika ndi telomere kutalika. Mwa odwala omwe ali ndi T2DM, CRP ndi fibrinogen anali okwera kwambiri mwa anthu omwe anali ndi telomeres lalifupi (p = 0.02). Poyerekeza magulu ndi ma telomeres “atali”, palibe kusiyana komwe kunapezeka pamlingo wa CRP (p = 0.93). Odwala omwe ali ndi matenda a shuga a mtundu wachiwiri komanso “otsika” telomerase, zovuta za kutupa kosatha zinali zazikulu. Odwala omwe ali ndi matenda a shuga a 2, ubale wapezeka pakati pa kutalika kwa telomere ndi CRP (r = -0.40, p = 0.004). Pomaliza Kutupa kosalekeza komanso kukalamba kwa maselo mwa odwala omwe ali ndi matenda a shuga a 2 amadziwika bwino kuposa momwe angayang'anire. Komabe, mwa odwala omwe ali ndi ma telomeres “atali,” zizindikiro za kutupa kosatha sizinasiyane kwambiri ndi zomwe zili mwa anthu athanzi. Mwinanso ma telomeres amtundu wautali amateteza odwala omwe ali ndi T2DM ku zowonongeka za kutupa kosalekeza.

Kutalika kwa Telomere, telomerase zochita ndi njira zimasintha mwa odwala omwe ali ndi matenda a shuga 2

Zolinga. Kuti muphunzire kuyanjana kwa matenda osachiritsika, oxidative nkhawa ndi telomere biology mwa anthu omwe ali ndi matenda a shuga 2: mellitus (T2DM). Zida ndi Njira. Odwala okwanira 50 omwe ali ndi T2D komanso opanda matenda a mtima (CVD) ndi anthu 139 ochokera pagulu lolamulira adaphatikizidwa phunziroli. Maphunziro onse adayezedwa a carbohydrate metabolism, oxidative stress (malondialdehyde (MDA)), kutupa (C-reactive protein CRP, fibrinogen, interleukin-6), lymphocyte telomere kutalika, ntchito ya telomerase. Zotsatira Mu odwala odwala matenda ashuga telomeres anali ofupikirapo kuposa maulamuliro (9.59 ± 0.54 ndi 9.76 ± 0.47, p = 0.031), ntchito ya telomerase inali yotsika (0.47 ± 0.40 ndi 0.62 ± 0.36, p = 0.039), kutupa (CRP, fibrinogen okwera) inali yayitali . Odwala onse anali ma div> telomere kutalika. Mu T2DM gulu CRP linali lokwera kwambiri kwa odwala omwe ali ndi ma “telomeres” amafupi (7.39 ± 1.47 ndi 3.59 ± 0.58 mg / L, p = 0.02). Panalibe kusiyana kwakukulu pamlingo wakutupa kwambiri komanso kupsinjika kwa oxidative mu gulu la ma 'telomeres nthawi yayitali: CRP 3.59 ± 0.58 ndi 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 ndi 3.24 ± 0.78 mmol / l ( p = 0.08). Odwala odwala matenda ashuga omwe ali mu gulu la "ma fupi" telomeres anali ndi kutupa kwakukulu: CRP 7.39 ± 1.47 ndi 4.03 ± 0.62 mg / L (p = 0.046), kuchuluka kwa fibrinogen, 0.371 ndi 0.159 (p = 0.022). Odwala onse anali ntchito ya div> telomerase. Kuopsa kwa kutupa kosatha kunali kwakukulu mu T2DM ndi "otsika" ntchito ya telomerase. Panali ubale pakati pa telomere kutalika ndi CRP mwa odwala T2DM (r = -0.40, p = 0.004). Mapeto. Kutupa kosalekeza komanso kukalamba kwa maselo kunatchulidwa kwambiri mwa odwala omwe ali ndi T2DM. Komabe, ngakhale anali ndi matenda ashuga, Zizindikiro za kutupa kosakhazikika zinali zochepa kwa odwala omwe ali ndi ma telomeres "atali" poyerekeza ndi anthu athanzi. Mwina ma telomeres autali amateteza odwala omwe ali ndi matenda ashuga ku zowonongeka za kutupa kosalekeza.

Zolemba za asayansi pankhani "Kutalika kwa Telomere, ntchito za telomerase, ndimayendedwe asinthidwe wawo wodwala wodwala matenda ashuga a 2"

Kutalika kwa Telomere, telomerase zochita ndi njira zawo zosinthira wodwala wokhala ndi matenda a shuga a 2

Ph.D. N.V. BRAYLOVA1 *, Ph.D. E.N. DUDINSKAYA1, MD O.N. TKACHEVA1, membala wolingana RAS M.V. SHESTAKOVA2, Ph.D. I.D. STRAZHESKO1, woyimira masayansi azachipatala D.U. AKASHEV1, E.V. PLOKHOVA1, V.S. Pykhtina1, V.A. VYGODIN1, prof. S.A. ZAMAKONI1

1 FSBI "State Research Center for Preventive Medicine", Moscow, Russia, 2 FSBI "Endocrinological Research Center" ya Unduna wa Zaumoyo ku Russia, Moscow, Russia

Cholinga cha phunziroli chinali kuphunzira za ubale wa kutupa kwakatundu, kupsinjika kwa oxidative, ndi telomere biology mwa anthu omwe ali ndi matenda a shuga 2 a mellitus (T2DM).

Zida ndi njira. Phunziroli lidaphatikizapo odwala 50 omwe ali ndi matenda a shuga a 2 popanda mawonekedwe a matenda amtima (CVD) ndi anthu a 139 pagulu lolamulira. Mkhalidwe wama metabolism a carbohydrate, kuchuluka kwa oxidative nkhawa (malondialdehyde - MDA) ndi kutupa kosatha (fibrinogen, mapuloteni a C-reactive - CRP, interleukin-6 - IL-6) anayesedwa, kutalika kwa ma lymphocyte telomeres ndi telomerase anayeza.

Zotsatira Odwala omwe ali ndi matenda a shuga a mtundu wa 2, kutalika kwa telomere kunali kochepa (p = 0.031), zochitika za telomerase zinali zochepa (p = 0.039), ndipo kuchuluka kwa kutupa (CRP ndi fibrinogen level) kunali kokulirapo kuposa pagulu lolamulira. Odwala onse adagawika ndi telomere kutalika. Mwa odwala omwe ali ndi T2DM, CRP ndi fibrinogen anali okwera kwambiri mwa anthu omwe anali ndi telomeres lalifupi (p = 0.02). Poyerekeza magulu ndi ma telomeres “atali”, palibe kusiyana komwe kunapezeka pamlingo wa CRP (p = 0.93). Odwala omwe ali ndi matenda a shuga a mtundu wachiwiri komanso “otsika” telomerase, zovuta za kutupa kosatha zinali zazikulu. Odwala omwe ali ndi matenda a shuga a 2, ubale wapezeka pakati pa kutalika kwa telomere ndi CRP (r = -0.40, p = 0.004).

Pomaliza Kutupa kosalekeza komanso kukalamba kwa maselo mwa odwala omwe ali ndi matenda a shuga a 2 amadziwika bwino kuposa momwe angayang'anire. Komabe, mwa odwala omwe ali ndi ma telomeres “atali,” zizindikiro za kutupa kosatha sizinasiyane kwambiri ndi zomwe zili mwa anthu athanzi. Mwinanso ma telomeres amtundu wautali amateteza odwala omwe ali ndi T2DM ku zowonongeka za kutupa kosalekeza.

Mawu ofunikira: kutalika kwa telomere, ntchito ya telomerase, matenda a shuga, kuperewera, kupsinjika kwa oxidative.

Kutalika kwa Telomere, telomerase zochita ndi njira zimasintha mwa odwala omwe ali ndi matenda a shuga 2

N.V. BRAILOVA1, E.N. DUDINSKAYA1, O.N. TKACHEVA1, M.V. SHESTAKOVA2, I.D. STRAZHESKO1, D.U. AKASHEVA1, E.V. PLOCHOVA1, V.S. PYKHTINA1, V.A. VYGODIN1, S.A. BOYTSOV1

'National Research Center for Preventive Medicine, Moscow, Russia, 2 Endocrinology Research Center, Moscow, Russia

Zolinga. Kuti muphunzire kuyanjana kwa matenda osachiritsika, oxidative nkhawa ndi telomere biology mwa anthu omwe ali ndi matenda a shuga 2: mellitus (T2DM).

Zida ndi Njira. Odwala okwanira 50 omwe ali ndi T2D komanso opanda matenda a mtima (CVD) ndi anthu 139 ochokera pagulu lolamulira adaphatikizidwa phunziroli. Maphunziro onse adayezedwa a carbohydrate metabolism, gulu la oxelomeres: CRP 3.59 ± 0.58 ndi 3.66 ± 0.50 mg / L (p = 0.93), MDA 2.81 ± 0.78 ndi 3.24 ± 0.78 mmol / l (p = 0.08). Odwala odwala matenda ashuga omwe ali mu gulu la "ma fupi" telomeres anali ndi kutupa kwakukulu: CRP 7.39 ± 1.47 ndi 4.03 ± 0.62 mg / L (p = 0.046), kuchuluka kwa fibrinogen, 0.371 ndi 0.159 (p = 0.022). Odwala onse anali div>

Mapeto. Kutupa kosalekeza komanso kukalamba kwa maselo kunatchulidwa kwambiri mwa odwala omwe ali ndi T2DM. Komabe, ngakhale anali ndi matenda ashuga, Zizindikiro za kutupa kosakhazikika zinali zochepa kwa odwala omwe ali ndi ma telomeres "atali" poyerekeza ndi anthu athanzi. Mwina ma telomeres autali amateteza odwala omwe ali ndi matenda ashuga ku zowonongeka za kutupa kosalekeza.

Mawu osakira: kutalika kwa telomere, ntchito ya telomerase, matenda a shuga, kutupa kosalekeza, kupsinjika kwa oxidative.

Kupsinjika kwa m'magazi ndi zotupa zosafunikira monga maziko a kukalamba kwachilengedwe

Matenda a shuga mellitus (DM) amayenda limodzi ndi kusintha kwamphamvu kwa mitsempha yamagazi, komwe kumapangitsa kukhala chifukwa chodwala matenda amtima (CVD) komanso kufa. Chiyanjano chachikulu cha data

zosintha - hyperglycemia, insulin kukana, kudzikundikira kwa zinthu zomaliza za glycation (CNG). Hyperinsulinemia ndi hyperglycemia, komanso kukalamba kwachilengedwe, zimayambitsa njira zotupa zosafunikira komanso kupsinjika kwa oxidative. M'thupi lokalamba, ngati

otsika odwala wodwala matenda ashuga, kuchuluka kwa mitundu yosiyanasiyana ya kutupa kumawonjezera C-reactive protein (CRP), IL-18, TNF-a ("kutupa"), kumawonjezera ntchito ya lipid peroxidation ndikupanga malondialdehyde (MDA) ndi mitundu yogwira mpweya wa oxygen (ROS) . Zonsezi zimayambitsa kusokonekera kwa mapuloteni, cell apoptosis ndi kukula kwa njira zoperewera.

Biology ya telomeres mwa anthu omwe ali ndi matenda ashuga 2

Chimodzi mwazifukwa zosiyanasiyana zakukalamba kwamankhwala kwa odwala omwe ali ndi matenda amtundu wa 2 ndiko "kutetezedwa kwa chibadwa" mosiyana ndi zinthu zakunja. Kutalika kwa telomere ndi telomerase kungatenge gawo la zolembera zam'mibadwo yamagazi. Ma Telomeres ndi magawo omaliza a molekyulu ya DNA yomwe imafupikitsidwa pang'onopang'ono ndi gawo lililonse la khungu. Kutalika kwa DNA ya telomeric kukakhala koopsa, P53 / P21, kukalamba kwa selo, kumasungidwa ndikusungabe zochitika zake za metabolic. Pali umboni wosonyeza kuti kutalika kwa ma telomeres mu leukocytes kumawonetsa kutalika kwa ma telomeres mu masentimita a tsinde ndipo amafanana ndi kutalika kwake m'maselo a endothelial progenitor, omwe amatilola kuwona gawo ili ngati biomarker ya kukalamba kwamankhwala. Zizindikiro zoyambira kufupikitsa kwa telomere mwa anthu omwe ali ndi matenda a shuga a 2 komanso kulekerera shuga adapezeka. Kufupikitsa kwa Telomere kungagwirizanitsidwe ndi kukula kwa T2DM, CVD ndi ukalamba wa mtima.

Chizindikiro chachiwiri cha kubereka chingakhale ntchito ya telomerase. Telomerase ndi enzyme yomwe imawonjezera kubwereza kwapadera kwa DNA panjira ya 3'-yomaliza ya DNA ndikuphatikizanso telomerase reverse transcriptase (TERT) ndi telomerase RNA (TERC). M'maselo ambiri amtundu wa telomerase ndizochepa kwambiri. Ngakhale telomerase simagwira gawo lofunikira mu telomere kutalika kwa homeostasis muukalamba, akukhulupirira kuti enzyme iyi imakhala ndi ntchito zomwe sizofunikira telomere kuti muchepetse apoptosis, kuwongolera kuchuluka kwa maselo, komanso zochitika za mitochondrial m'maselo a anthu.

Udindo wa kutupa kwambiri ndi oxidative

nkhawa pakusintha kwa telomere kutalika ndi ntchito

telomerase mwa anthu odwala matenda ashuga amtundu wa 2

Zoyambitsa zazikulu za pathological zomwe zimakhudzana ndi ukalamba pamaselo a cellular zimawonedwa ngati kupsinjika kwa oxidative komanso kutupa kwakanthawi, zomwe zimapangitsa kufupikitsa kwa DNA. Telomere Zomvera

Amayambitsa oxidative kuwonongeka kwa molekyulu ya DNA. In vitro ROS imachepetsa mapuloteni a nyukiliya a hTERT m'maselo a endothelial ndipo, motero, telomerase zochita. Telomerase imatha kuteteza maselo oyera pamagazi oxidative osakhudza kutalika kwa ma telomeres. Kuchulukitsa kwa ntchito kumathandizira kufupikitsa kwa telomeres onse chifukwa cha kuchulukitsa kwa kuchuluka kwa maselo, komanso chifukwa chakumasulidwa kwa ROS. Kuchepetsa kwapang'onopang'ono kwa ma telomeres ndikuwonjezeka kwa nthawi ya T2DM kumatha kuphatikizidwa ndi kupsinjika kwakanthawi komanso kupsinjika kwa oxidative. Chibale pakati pa ntchito za telomerase ndi kutupa kosaphatikizika kusakanikirana. Kutupa kwakadali koyambirira kudzera m'njira zosiyanasiyana (monga NF-kB, protein kinase C kapena Akt kinase) kudzera mu phosphorylation kapena kulemba kwa hTERT kumatha kuyambitsa telomerase, yomwe,

Zambiri za alembi:

Brailova Natalia Vasilievna - Ph.D. Dep.kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka zakale a State Research Center for Preventive Medicine, Moscow, Russia, imelo: [email protected],

Dudinskaya Ekaterina Nailevna - woyimira masukulu azachipatala, wothandizira wamkulu wasayansi Dep. kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka za Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia,

Tkacheva Olga Nikolaevna - MD, prof., Manja. Dep. kuphunzira njira za ukalamba ndi kupewa matenda okhudzana ndi zaka FSBI State Research Center for Preventive Medicine, Moscow, Russia, Shestakova Marina Vladimirovna - membala wofanana. RAS, Director of the Institute of Diabetes, Wachiwiri mbawala Ntchito yasayansi ya Federal State Budgetary Institution "Endocrinological Science Science Center", Moscow, Russia, Strazhesko Irina Dmitrievna - woimira wasayansi wazachipatala, wofufuza wamkulu Dep. kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka za Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia,

Akasheva Dariga Uaydinichna - woimira masayansi azachipatala, wofufuza wamkulu Dep. kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka za Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia,

Plokhova Ekaterina Vladimirovna - woyimira masayansi azachipatala, wofufuza wamkulu Dep. kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka za Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia,

Pykhtina Valentina Sergeevna - labu. Dep. kuphunzira kukalamba ndi kupewa matenda okhudzana ndi zaka za Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia,

Vygodin Vladimir Anatolyevich - wofufuza wamkulu labu. biostatistics Federal State Budgetary Institution "State Research Center for Preventive Medicine", Moscow, Russia, Sergey Anatolyevich Boytsov - MD, pulofesa, manja. Dep. Cardiology ndi Molecular Genetics, Director, State Research Center for Preventive Medicine, Moscow, Russia

Piyano, amalipira kufulumira kwa kufulumira kwa zolimbitsa thupi. Komabe, kumapeto kwa ulesi, ntchito ya telomerase imachepa, zomwe zimayambitsa kufupikitsa kwa ma telomeres.

Cholinga cha phunziroli chinali kuphunzira za ubale wamafinya komanso nkhawa za oxidative ndi telomere biology mwa anthu omwe ali ndi matenda a shuga a 2.

Zida ndi njira

Kafukufuku wokhudzana ndi gawo limodzi adaphatikizapo odwala omwe ali ndi matenda ashuga a 2 omwe adayesedwa kunja kwa Federal State Budget Science Science Center for Surgery mu 2012-2013. Gulu lalikulu linali ndi odwala azaka zapakati pa 45 mpaka 75 omwe ali ndi matenda osapitilira miyezi 12 komanso HbA1c ili ndi 6.5 mpaka 9.0%. Gulu lowongolera lidaphatikizapo anthu opanda T2DM omwe analibe chiwonetsero chachipatala cha CVD, omwe adatembenukira kuchipatala kuti apatsidwe uphungu.

Njira zochotsera: mtundu 1 wa matenda ashuga ndi mitundu ina ya matenda ashuga, giredi 3 ochepa matenda oopsa (kuthamanga kwa magazi) (kuthamanga kwa magazi> 180/100 mm Hg), kugwiritsa ntchito pafupipafupi mankhwala opatsirana a antihypertensive, kugwiritsa ntchito mankhwala a antihypertensive, michereopathies yodwala kwambiri kuchuluka kwa odwala matenda ashuga retinopathy, matenda a impso a magawo 3b, 4 ndi 5), CVD (mtima wosalephera, magiredi II - IV (NYHA), matenda a mtima osakhazikika), kuperewera kwa chiwindi, khansa, kutenga pakati, kuyamwa.

Odwala onse adasaina chilolezo chokhala nawo nawo phunziroli. Phunziroli linavomerezedwa ndi komiti yakakhalidwe kazachipembedzo ya FSBI GNITsPM ya Ministry of Health of Russia. Protocol yamisonkhano ya LEK No. 8 ya 11.29.11.

Pakuwunika, odwala onse adayeza mayeso a zamankhwala: kuyesedwa kwa mbiriyakale, kuyezetsa zamankhwala, kuphatikiza muyeso wa thupi ndi kutalika ndi mawerengedwe am'munsi index (BMI), muyeso wa systolic (SBP) ndi diastolic magazi (DBP) pachipangizo chowerengera kugwiritsa ntchito phewa la mapewa (HEM-7200 M3, Omron Healthcare, Japan). Kuthamanga kwa magazi kunayesedwa pambuyo pakupumula kwa mphindi 10 kudzanja lamanja kukhala pampando katatu patatha mphindi ziwiri, pafupifupi magawo atatu adaphatikizidwa pakuwunikanso. Magazi adatengedwa kuti adziyese ngati a labotale (a kliniki ndi a biochemical), ECG idalembedwa, ndipo kuyesedwa kochita masewera olimbitsa thupi kunachitidwa pa mayeso olimbitsa thupi pogwiritsa ntchito BRUCE protocol (Intertrack, SCHILLER). Mwa odwala 250 omwe adawunika, 189 adakwaniritsa njira zophatikizira. Mkhalidwe wama metabolism a carbohydrate adayesedwa mwa iwo onse, kutalika kwa telomere ndi ntchito ya telomerase adatsimikiza, ndikuvuta kwa oxidative kupsinjika ndi kutupa kosatha kudalembedwa.

Carbohydrate kagayidwe

Kuphatikizika kwa shuga m'magazi a plasma kunatsimikiziridwa ndi njira ya glucose oxidase pa SAPPHIRE-400 piritsi ya DiaSys diagnostic zida. Mulingo wa HbA1c unalembedwa ndi ma chromatography amadzimadzi pa Sapphire 400 analyzer (Niigata Mechatronics, Japan) molingana ndi momwe wopanga amapangira.

Kuyeza kwa Kutalika kwa Telomere

Muyezo wa kutalika kwofananira kwa ma telomeres a zotumphukira za m'mimba zimachitika pa genomic DNA. Pakusanthula kwa PCR kwenikwenidi, kuchuluka kwa DNA yokhala ndi ma telomeric mu genome akuti. Mofananamo, PCR yeniyeni yochitika idachitidwa pa kope limodzi la genomic DNA. Tidachoka motengera kuchuluka kwa chiwerengero cha ma telomeric ndi matepi amodzi mpaka kutalika kwa ma telomeres.

Kuyeza kwa ntchito ya telomerase

Kuti mudziwe ntchito ya telomerase, njira yomwe idasinthidwa idagwiritsidwa ntchito. Ntchito ya enzyme idafufuzidwa mumagulu osankhidwa a ma cell am'magazi (pafupifupi maselo 10,000 pakuwunika). Maselo a Monocyte adamangidwa ndi chosungira chofewa, ndikulekanitsa zochotsazo. Machitidwe a telomerase polymerase adachitika ndi Tingafinye; zinthu zomwe zidapezekazo zidakulitsidwa ndi PCR yeniyeni. Kuchuluka kwa zinthu zopanga telomerase ndizofanana ndi zochitika za telomerase (Mastercyulin amplifier (Eppendorf, Germany).

Kuyesa Kwamavuto Oxidative

Kuti muwone kukula kwa kupsinjika kwa oxidative, kuchuluka kwa MDA kunaphunziridwa ndi njira ya luminol-based hemiluminescence m'mwazi wathunthu.

Kuyesa kwa kutupa kosatha

Kuti tiwone kuwonongeka kwa matenda osachiritsika, taphunzira kuchuluka kwa mtundu wa fibrinogen, njira yovuta kwambiri ya C-reactive protein (CRP) (njira ya immunoturbodimetric pogwiritsa ntchito njira ya SAPPHIRE-400), IL-6 (immuno-enzyme).

Kutsata ndi biomedical Ethics

Phunziroli lidachitika mogwirizana ndi miyezo ya Good Clinical Practice ndi mfundo za Helsinki Declaration. Phunziroli linavomerezedwa ndi Ma Komiti a Ethics a magulu onse omwe atenga nawo mbali pazachipatala. Asanaphatikizidwe mu kafukufukuyu

Onse omwe analandila adalandira chidziwitso cholemba.

Tidagwiritsa ntchito mapulogalamu omwe amagwiritsidwa ntchito polemba manambala SAS 9.1 (Statistical Analysis System, SAS Institute Inc., USA). Zambiri zinayikidwa mu processor ya tabular, pambuyo pake kuwunika koyeserera kunachitika kuti muwone zolakwika zakuyika ndi mfundo zosoweka. Kwa magawo ochulukitsa, kuyesa kwa asymmetry ndi kurtosis kunagwiritsidwa ntchito, zomwe zinawululira magawidwe apamwamba a magawo ambiri. Zambiri zimafotokozedwa ngati zofunikira komanso zopatuka (M ± SD). Zomwe amatanthauza zakufunika kwa magawo azachipatala adaziyerekeza m'magulu awiri pogwiritsa ntchito njira imodzi yosinthira mosinthasintha mosiyanasiyana ndi mtundu wa x2 pazosintha zamagulu. Pazowonetsa pafupipafupi, mawonekedwe a Student mod osinthidwa amagwiritsidwa ntchito poganizira kusintha kwa Fcsher arcsin. Kuti muwone mgwirizano wa mzere pakati pa magawo, kuwunika kosakanikirana (kuwongolera kwa mawonekedwe a Spearman) kunachitika. Kuyesa kuyanjana kodziyimira pakati pa magawo, kuyerekezera kwamitundu yambiri komanso kusanthula kwakanthawi kogwiritsa ntchito kunagwiritsidwa ntchito. Pambuyo poyeza kutalika kwa telomere, magawo owonjezera a odwala m'magulu amodzi adachitika molingana ndi mfundo zofunika kwambiri. Gulu loyamba lili ndi odwala omwe ali ndi telomere lalifupi kwambiri: kuchokera pamtengo wofunikira kwambiri mpaka malire a gawo loyambirira (mwachitsanzo 25% ya malire ogawa). Gulu lachiwiri lomwe lidaphatikizidwa lidaphatikizapo odwala omwe ali ndi ma telomere kutalika kuchokera pakugawika kwapakatikati mpaka pazing'onoting'ono. Gulu lachitatu lili ndi odwala omwe amakhala ndi ma telomere kutalika kuchokera pakugawika kwapakati mpaka 75% ya malire ogawa. Anthu okhala ndi telomere lalitali kwambiri, omwe amapanga gawo lalikulu kwambiri la magawikidwe, adapatsidwa gulu lazinayi. Zongoganiza zopanda ntchito zidakanidwa pa p Sindingapeze zomwe mukufuna? Yeserani ntchito yosankha mabuku.

Odwala onse 189 (amuna 64 ndi akazi a 125) adaphatikizidwa mu phunziroli, omwe adaphatikizidwa m'magulu awiri: ndi T2DM (i = 50) komanso popanda matenda a shuga (i = 139). Kutalika kwa T2DM kunali zaka 0.9 + 0.089. Avereji ya odwala omwe ali ndi matenda a shuga a 2 anali zaka 58.4 ± 7.9, ndi gulu loyang'anira - zaka 57.45 + 8.14 (p = 0.48). Mu gulu la SD2, SBP inali 131.76 + 14.7 mm Hg, ndipo pagulu lolamulira - 127.78 + 16.5 mm Hg. (p = 0.13). Mulingo wa MDA mu gulu la T2DM anali 3.193 + 0.98 μmol / L, ndipo pagulu loyang'anira anali 3.195 + 0.82 μmol / L (p = 0.98). Mulingo wamba wa IL-6 pagulu la T2DM anali 3.37 + 1.14 pg / ml, pagulu lolamulira anali 5.07 + 0.87 pg / ml (p = 0.27).

Mu gulu la anthu odwala matenda ashuga, gawo la amuna linali lokwera kuposa gulu la anthu athanzi (46% motsutsana 29%) (p = 0.013). Chiwerengero cha amuna ndi akazi pagulu la T2DM chinali 46/54% motsutsana ndi 29/71% pagulu lolamulira (^ = 0.013). BMI ya odwala omwe ali ndi matenda a shuga a 2 anali kwambiri poyerekeza ndi anthu athanzi: 30.28 ± 5.42 motsutsana ndi 27.68 ± 4.60 kg / m2 (p = 0.002). DBP pagulu la T2DM inali 83.02 ± 11.3 mm Hg. motsutsana 78.6 ± 9.3 mmHg pagulu lolamulira (p = 0.015). Odwala omwe ali ndi matenda a shuga a 2, kutalika kwa ma lymphocytic telomeres kunali kochepa kwambiri (p = 0.031), ndipo ntchito ya telomerase inali yotsika kwambiri (p = 0.039) kuposa anthu athanzi. Mu gulu la T2DM, kuthamanga kwa plasma glucose (GPN) ndi HbA1c anali okwera kwambiri kuposa gulu lolamulira (p sindikutha kupeza zomwe mukufuna? Yesani ntchito yosankha mabuku.

mer 9.59 + 0.54 9.76 + 0.47 0.031

Ntchito ya Telomerase 0.47 + 0.40 0.62 + 0.36 0.039

MDA, μmol / L 3.19 + 0.98 3.20 + 0.82 0.98

IL-6, pg / ml 3.37 + 1.14 5.07 + 0.87 0.27

CRP, mg / L 6.34 + 1.06 3.82 + 0.41 0.031

Fibrinogen, g / l 3.57 + 0.87 3.41 + 0.54 0.23

fibrinogen 0,30 + 0,04 0.11 + 0,03 0,004

Mndandanda wa 2. Chizindikiro cha metabolism ya carbohydrate, kupsinjika kwa oxidative, kutupa kosagwirizana, kutalika kwa telomere ndi telomerase, kutengera kukhalapo kwa T2DM

SD2 + ("= 50) ___ SD2- (" = 139)

Miyeso yayitali yamiyeso ("= 15) miyeso yayifupi ya thupi (" = 35) Milingo yayitali yotalikirapo ("= 76) miyeso yayifupi ya thupi (" = 63) P

HbA1c,% 11.54 + 3.57 13.48 + 3.24 0.072 10.98 + 1.83 11.59 + 2.03 0.075

GPN, mmol / L 0.83 + 0.13 0.95 + 0.17 0.02 0.76 + 0.16 0.78 + 0.14 0.59

MDA, μmol / L 2.81 + 0.78 3.35 + 1.04 0.09 3.24 + 0.78 3.14 + 0.87 0.58

CRP, mg / L 3.59 + 0.58 7.39 + 1.47 0.02 3.66 + 0.50 4.07 + 0.68 0.63

Fibrinogen, g / l 3.39 + 0.55 3.70 + 0.91 0.15 3.38 + 0.53 3.44 + 0.55 0.50

Kupezeka kwa kuchuluka kwa fibrinogen 0.143 0,371 0,09 0,09,09,09,09

IL-6, pg / ml 5.95 + 3.89 2.43 + 0.51 0.39 5.70 + 1.31 4.41 + 1.08 0.45

Ntchito ya Telomerase 0.51 + 0.09 0.47 + 0.08 0.78 0.60 + 0.05 0.66 + 0.07 0.42

"Low" telomerase zochita 0.417 0.710 0.09 0.512 0.474 0.73

Tebulo 3. Zizindikiro za oxidative nkhawa, kutupa kosatha ndi telomerase kutengera kutalika kwa malezala

Ma telomeres achidule

Parame SD2 + ("= 15) SD2- (" = 76) P SD2 + ("= 35) SD2- (" = 63) P

MDA, μmol / L 2.81 + 0.78 3.24 + 0.78 0.08 3.35 + 1.04 3.14 + 0.87 0.35

CRP, mg / L 3.59 + 0.58 3.66 + 0.50 0.93 7.39 + 1.47 4.03 + 0.62 0.046

Fibrinogen, g / l 3.39 + 0.55 3.38 + 0.53 0.95 3.70 + 0.91 3.44 + 0.55 0.135

Kupezeka kwa kuchuluka kwa fibrinogen 0.143 0.069 0.40 0.371 0.159 0.022

IL-6, pg / ml 5.94 + 3.89 5.70 + 1.31 0.94 2.43 + 0.51 4.41 + 1.08 0.10

Ntchito ya Telomerase 0.51 + 0.09 0.60 + 0.05 0.36 0.47 + 0.08 0.62 + 0.07 0.063

"Low" telomerase ntchito 0.512 0.417 0.56 0.710 0.474 0.049

Mndandanda wa 4. Chizindikiro cha metabolism ya carbohydrate, kupsinjika kwa oxidative, kutupa kosatha, kutalika kwa telomere ndi telomerase shughuli (AT), kutengera kukhalapo kwa T2DM

Parame SD2 + SD2- R

mkulu AT otsika AT P mkulu AT otsika AT

HbA1c,% 7.19 + 0.60 7.36 + 0.80 0.45 5.19 + 0.58 5.35 + 0.41 0.16

GPN, mmol / L 7.55 + 1.40 8.47 + 1.79 0.09 5.17 + 0.51 5.33 + 0.44 0.14

MDA, μmol / L 2.93 + 0.90 3.23 + 1.01 0.34 3.06 + 0.93 3.34 + 0.72 0.25

IL-6, pg / ml 2.98 + 1.01 3.91 + 2.03 0.68 3.77 + 1.00 6.37 + 1.80 0.21

CRP, mg / L 5.34 + 1.40 7.12 + 1.76 0.43 4.14 + 0.78 2.55 + 0.26 0.06

Fibrinogen, g / l 3.62 + 0.70 3.66 + 0.85 0.87 3.60 + 0.50 3.37 + 0.43 0.034

Kukhalapo kwa micrinogen yowonjezereka 0,375 0.259 0.43 0.205 0.075 0.09

Achibale telomere kutalika 9.77 + 0.50 9.43 + 0.42 0.02 9.81 + 0.51 9.70 + 0.45 0.33

odwala athanzi pakati pa anthu omwe ali ndi "lalifupi" ndi "marefu" ma telomeres, panalibe kusiyana kwakukulu pokhudzana ndi carbohydrate metabolism, kuopsa kwa oxidative nkhawa, komanso kutupa kwakanthawi (Table 2).

Odwala omwe ali ndi T2DM ndi ma "telomeres" afupiafupi, kuchuluka kwa CRP kunali kokulirapo ndipo kuwonjezeka kwa fibrinogen kunali kofala. Zosiyana m'magulu a MDA, fibrinogen, IL-6 sizinapezeke. Ntchito ya Telomerase inali yotsika pang'ono mwa odwala omwe ali ndi matenda a shuga a 2 komanso ma telomeres amfupi (9 = 0.063). Zizindikiro "zochepa" za telomerase zochitika zimapezeka kwa odwala omwe ali ndi T2DM komanso "zazifupi" miyeso ya thupi pafupipafupi kwambiri (9 = 0.049).

Mwa anthu omwe amakhala ndi ma telomeres amtundu, zolembera zamatenda osagonjetseka komanso oxidative nkhawa, komanso ntchito ya telomerase, anali palokha popanda T2DM (Table 3).

Ntchito ya Mediel telomerase inali 0,50. Odwala onse omwe ali ndi mtengo wotsikirapo wa chizindikirochi amapatsidwa gulu la "otsika" telomerase zochitika, ndi iwo omwe ntchito yawo ya telomerase imaposa mtengo uwu, ku gulu la "mkulu" telomerase ntchito. Odwala omwe ali ndi matenda a shuga a 2, mkhalidwe wama metabolism owonjezera, zochitika za zokhala ndi zovuta za oxidative komanso kutupa kwakanthawi sizinasiyane pakati pama magulu awa, kupatula ma telomeres amafupikitsa m'gululi omwe ali ndi "otsika"

telomerase (p = 0.02). Gulu lowongolera silinawunikenso kudalira kwa milingo yama oxidative, CRP ndi IL-6 pa zochitika za telomerase, komabe, anthu omwe ali ndi "mkulu" telomerase zochita adawonetsa milingo yayikulu ya fibrinogen (Table 4).

Odwala omwe ali ndi T2DM ndi "otsika" telomerase zochitika, CRP inali yochulukirapo, kuchuluka kwa fibrinogen kunali kofala, ndipo kutalika kwa telomere kunali kochepa. Miyezo ya IL-6, MDA ndi fibrinogen pagulu la "otsika" telomerase zochitika sizinadalire kukhalapo kwa T2DM. Mu gulu la "mkulu" telomerase zochita, nkhope za T2DM + ndi T2DM sizinasiyane ndi kupsinjika kwa oxidative, kutupa kwakatundu, komanso kutalika kwa telomere (Table 5).

Odwala omwe ali ndi T2DM, mayanjano amapezeka pakati pa kutalika kwa telomeres ndi GPN, CRP, "otsika" telomerase zochitika, koma kulumikizana sikunapezeke ndi ukalamba, kuthamanga kwa magazi, BMI, HLA1c MDA, fibrinogen, ndi IL-6 (Table 6).

Mu gulu la CD2 +, kuwongolera koyenera kunapezeka pakati pa zochita za telomerase ndi kutalika kwambiri kwa telomere. Mu gulu loyendetsa, zochitika za telomerase zinali zogwirizana ndi SBP, DBP, CRP ndi kuchuluka kwa fibrinogen (Table 7).

Pambuyo pake, kuwunika kosinthika kwa mzere zingapo kunachitika, komwe kutalika kwa ma telomeres kunagwiritsidwa ntchito ngati mtundu wodalirika, ndipo m'badwo, GPN, CRP, ndi "otsika" telomerase ntchito adagwiritsidwa ntchito ngati mitundu yosayimira pawokha. Zidadziwika kuti GPN ndi CRP zokha zomwe zimagwirizanitsidwa modekha ndi kutalika kwa telomere (Gawo 8).

Mukamagwiritsa ntchito telomerase ngati odalira osinthika, komanso ngati odziyimira pawokha - DBP, GPN, CRP, fibrinogen, zidapezeka kuti mu gulu la CD2, DBP (mayankho) ndi fibrinogen (yolumikizana mwachindunji) okha omwe adalumikizana ndi ntchito ya telomerase ( tebulo 9). Mu gulu la CD2 +, panalibe ubale wodziyimira pakati pa magawo omwe adaphunziridwa ndi telomerase shughuli (Gome 10).

Tidapeza kuti odwala omwe ali ndi matenda ashuga a 2, kutalika kwa kayendedwe ka thupi kumakhala kakafupi kwambiri kuposa kwa anthu athanzi. Ndi

Tebulo 6. Chibale cha telomere kutalika ndi magawo ena m'magulu omwe aphunziridwa (malumikizidwe a malo a Spearman)

SD2 + (n = 50) SD2- (n = 139) kutalika kwa telomere kutalika

Zaka, zaka -0.09, p = 0.52 -0.18, p = 0.035

GARDEN, mmHg -0.036, p = 0.81 -0.14 p = 0.09

DBP, mmHg 0.066, p = 0.65 -0.03 p = 0.75

BMI, kg / m2 -0.025, p = 0.87 -0.13 p = 0.13

GPN, mmol / L -0.42, p = 0.0027 -0.16 p = 0.05

HbA1c,% -0.23, p = 0.12 -0.03 p = 0.69

MDA, μmol / L -0.17, p = 0.24 0.07, p = 0.55

CRP, mg / L -0.40, p = 0.004 -0.05 p = 0.57

Fibrinogen, g / l -0.18, p = 0.22 -0.04 p = 0.65

IL-6, pg / ml -0.034, p = 0.82 -0.04 p = 0.68

Ntchito ya Telomerase 0.15, p = 0.33 0.03, p = 0.78

Kuchita masewera olimbitsa thupi “Otsika”

kuphatikiza -0.32, p = 0.035 -0.06, p = 0.61

Gome 7. Zomwe zikugwirizana ndi zochitika za telomerase ndi magawo ena m'magulu omwe aphunziridwa (malumikizidwe a malo a Spearman

Zochita za telomerase SD2 + (n = 50) SD2- (n = 139)

Zaka, zaka za GARDEN, mm Hg DBP, mmHg BMI, kg / m2 GPN, mmol / L НАА1с,% MDA, μmol / L SRB, mg / L

Kukhalapo kwa CRP Fibrinogen, g / l IL-6, PG / ml

Kutalika kwamitundu yoyesera

Zochita zolimbitsa thupi zazitali kwambiri

5, p = 0.35 2, p = 0.44 4, p = 0.37 -0.07, p = 0.65 -014, p = 0.38 -0.08, p = 0.64 - 0.064, p = 0.69 0.056, p = 0.73 0.03, p = 0.89-0.086, p = 0.59-0.006, p = 0.97

0.07, p = 0.52 0.20, p = 0.08 0.33, p = 0.003

-0,04 -0,17 -0,08 -0,11

p = 0.72 p = 0.14 p = 0.47 p = 0.47

0.11, p = 0.35 0.35, p = 0.002 0.28, p = 0.01 -0.19, p = 0.12

0.15, p = 0.33 0.03, p = 0.78 0.40, p = 0.0095 0.14, p = 0.22

zogwirizana ndi zotsatira za olemba ena. Komabe, mu kafukufuku wolemba M. Sampson et al. palibe ubale womwe udapezeka pakati kufupika kwa kutalika kwa ma lymphocytic telomeres ndi zizindikiro za kagayidwe kazakudya (mwina chifukwa cha chiwerengero chochepa cha

Tebulo 5. Zizindikiro za oxidative nkhawa, kutupa kosatha komanso kutalika kwa ma telomeres kutengera ntchito ya telomerase (AT)

Paramenti Yotsika AT AT AT

SD2 + SD2- r SD2 + SD2- r

MDA, μmol / L 3.23 + 1.01 3.34 + 0.72 0.68 2.93 + 0.90 3.06 + 0.93 0.68

IL-6, pg / ml 3.91 + 2.03 6.37 + 1.80 0.37 2.98 + 1.01 3.77 + 1.00 0.62

CRP, mg / L 7.12 + 1.76 2.55 + 0.26 0.016 5.34 + 1.40 4.14 + 0.78 0.44

Fibrinogen, g / l 3.66 + 0.85 3.37 + 0.43 0.11 3.62 + 0.70 3.60 + 0.50 0.90

Kupezeka kwa kuchuluka kwa fibrinogen 0,259 0,06 0,03 0,375 0.205 0.21

Achibale telomere kutalika 9.43 + 0.42 9.70 + 0.45 0.016 9.77 + 0.50 9.81 + 0.51 0.80

Tebulo 8. Kudalira kwa kutalika kwa telomere pa msinkhu, GPN, CRP, kunachepetsa zochitika za telomerase ngati zosintha zodziwika bwino kwa odwala omwe ali ndi matenda a shuga a 2

Kulakwitsa kwa Paramu B P

Zaka, zaka -0.0008 -0.008 0.92

GPN, mmol / L -0.076 0.036 0.004

CRP, mg / L -0.018 0.007 0.020

Zochita "zochepa"

nthawi -0.201 0.125 0.116

Tebulo 9. Kudalira kwa ntchito ya telomerase pazaka, DBP, GPN, CRP, fibrinogen, GPN ngati zosintha pawokha pagulu lolamulira

Kulakwitsa kwa Paramu B P

Zaka, zaka -0.003 0.005 0.534

DBP, mmHg -0.010 0.004 0.012

GPN, mmol / L -0.105 0.081 0.20

CRP, mg / L 0.019 0.010 0.073

Fibrinogen, g / l 0,205 0.080 0,013

Gome 10. Kudalira kwa ntchito ya telomerase pazaka, DBP, GPN, CRP, fibrinogen, GPN ngati zosinthika palokha pagulu la odwala omwe ali ndi matenda a shuga a 2

Kulakwitsa kwa Paramu B P

Zaka, zaka 0.002 0.008 0.74

DBP, mmHg -0.0001 0.006 0.98

GPN, mmol / L -0.006 0.039 0.15

CRP, mg / L 0.007 0.009 0.45

Fibrinogen, g / l -0.009 0.089 0.91

Gulu la STI). Kafukufuku wathu adawonetsa kusiyana kwakukulu mu HbA1c ndi GPN mwa odwala T2DM omwe ali ndi ma "telomeres" a nthawi yayitali komanso "lalifupi", komanso adapeza ubale wosagwirizana pakati pa kutalika kwa telomere ndi GPN. Titha kunena kuti odwala omwe ali ndi matenda a shuga a mtundu wachiwiri, ma telomeres afupiafupi amagwirizanitsidwa ndi kuyendetsa bwino matenda a shuga, komanso hyperglycemia, iwonanso imatha kuwononga kukalamba.

Tidapeza kuti ntchito ya telomerase kwa odwala omwe ali ndi matenda a shuga 2 ndi yotsika kuposa mwa anthu athanzi, zomwe ndizogwirizana ndi zochepa zomwe zilipo. Udindo wa telomerase paukalamba wabwino umakhala wophunzirira komanso wosaphunzira. Sitinawululire ubale pakati pa zochitika za telomerase ndi kutalika kwa telomere, zomwe zimagwirizana ndi lingaliro lakuti gawo la telomerase ndilosakwanira kusunga telomere kutalika kwa homeostasis muukalamba.

Mavuto owononga a hyperglycemia pa biology ya telomeres, kuphatikizapo maselo a endothelial, amadziwika kudzera mu kupangika kwa oxidative nkhawa komanso kutupa kosatha. Komabe, zofunikira

Panalibe kusiyana kulikonse pamlingo wa MDA pakati pa magulu a T2DM + ndi T2DM (mwina chifukwa cha nthawi yochepa ya matenda ashuga komanso kusakhalapo kwa hyperglycemia yayitali, popeza hyperglycemia yotalika nthawi yayitali imalumikizidwa ndi kukhazikika kwa kupsinjika kwa oxidative koopsa. Pangakhale kofunikira kugwiritsa ntchito zowonetsera zowonjezereka za kupsinjika kwa oxidative, monga kwamikodzo excretion ya 8-iso-prostaglandin F2a. Tidapeza ziwonetsero zambiri za odwala omwe ali ndi matenda a shuga 2 kuposa omwe ali m'gululi. Chizindikiro china chotupa, IL-6, monga momwe chidawululidwira posachedwa, chimakhala ndi zotsatira zingapo, sichokhala cytokine yokha, komanso myokine, yolimbikitsa myogeneis komanso zimapindulira moyenera metabolism. Mwina ndichifukwa chake mulingo wa IL-6 muulamulirowo unakhala wokwera kwambiri, womwe, komabe, umafunanso kuphunzira kwina.

Kutupa kosatha kumayambitsa kukalamba kwa maselo, telomere kufupikitsa ndikuwonjezera kuchuluka kwa maselo a lymphocytic ndikuyambitsa kutulutsidwa kwa ROS, ndikupangitsa kuwonongeka kwa oxidative ku gawo la DNA. Mu 2012, zidawonetsedwa kuti kufupika kwapang'onopang'ono kwa ma telomeres okhala ndi kuwonjezereka kwa nthawi ya T2DM kungaphatikizidwe ndi kuwonjezereka kofanana kwa kupsinjika kwa oxidative ndi kutupa kosatha. Zotsatira zathu ndizogwirizana ndi kafukufuku wakale. Tidapeza milingo yayikulu kwambiri ya CRP komanso miyezo yapamwamba kwambiri ya MDA mwa odwala omwe ali ndi matenda ashuga a 2 komanso ma telomeres achidule kuposa odwala omwe ali ndi ma telomeres atali. Panali ubale wopanda pake pakati pa kutalika kwa lymphocyte telomere ndi chikhazikitso chapakatikati cha matenda osachiritsika - CRP, zomwe zikuwonetsa kutengapo gawo pakukhumudwa kwapang'onopang'ono kwa telomere kufupikitsa kwa odwala omwe ali ndi matenda a shuga a 2. Mu gulu loyendetsa, panalibe ubale pakati pa CRP ndi telomere kutalika, komwe kumagwirizana ndi maphunziro ena. Kulephera kuyankhulana pakati pa IL-6, fibrinogen, ndi kutalika kwa telomere m'magulu onsewa kumatha kufotokozedwa ndi kusinthasintha kochepa kwa zizindikirozi. Komanso, kungodalira kuchuluka kwa ma cytokines ozungulira, munthu akhoza kuchepetsa mphamvu ya kutukusira kwanuko m'thupi.

Zomwe mabuku amafotokoza pa ubale wa kutupa kosatha ndi ntchito ya telomerase ndizotsutsana. Kutalika kwa nthawi yayitali kumabweretsa kufooka kwa telomerase, yomwe tidawona odwala omwe ali ndi matenda a shuga 2. Ndi kutupa kocheperako komanso kwanthawi yayitali, monga momwe zimakhalira ndi metabolic syndrome kapena atherosulinosis, m'malo mwake, pali kuwonjezeka kwa zochitika za telomerase, zomwe mwina ndizobwezerera mwachilengedwe, ndikuchepetsa kuchepa kwa kutalika kwa telomere m'magawo

motsogozedwa ndi cytokines yotupa. Zowonadi, gulu loyang'aniranali, tidapeza ubale wabwino pakati pa zochitika za telomerase ndi chizindikiro cha kutupa kosatha.

Ndikofunikira kutsindika kuti, malinga ndi kuchuluka kwa deta yathu, kuchuluka kwa kuphatikiza kwa oxidative, kutupa kwakanthawi ndi zochitika za telomerase kwa odwala omwe ali ndi T2DM ndi ma telomeres a "yayitali" sizinasiyane kwambiri ndi ma indices omwe amagwirizana. Titha kuganiziranso kuti kutalika kwa T2DM, kutalika kwa nthawi yayitali kuteteza odwala ku zowonongeka za kupsinjika kwa oxidative komanso kutupa kwakatundu, kupereka kubwezeretsa bwino komanso kufulumira kwa ziwalo zowonongeka, kuphatikizapo mitsempha yamagazi. Mosiyana ndi izi, odwala omwe ali ndi T2DM komanso ma "telome" afupikitsa, ngakhale atatenga nthawi yochepa matendawa, kuwopsa kwa kutupa kosatha komanso kuchepa kwa ntchito ya telomerase kunali kofunika kwambiri. Tiyenera kudziwa kuti odwala matenda amtundu wachiwiri wa shuga ndi kuwongolera anali ofanana ndi msinkhu.

Pali umboni womwe ukukula kuti kufupikitsa kwa telomere ndichinthu chofunikira kwambiri pakuchepetsa malo osungirako masentimita ndikuwonongeka kwa minyewa yokhudzana ndi zaka. Kuyanjana kwa T2DM ndimayendedwe a kukalamba kwa maselo komanso kuopsa kwa kutupa kwakanthawi ndi kupsinjika kwa oxidative kungathe kufotokozera kuchuluka kwa CVD pamatendawa. Maphunziro owonjezerawa amalola kuganizira kutalika kwa telomere pakati pa odwala omwe ali ndi matenda a shuga a 2, gulu la anthu omwe amafunikira kwambiri kagayidwe kazakudya, komwe kangapereke njira yochiritsira matendawa.

1. Odwala omwe ali ndi matenda a shuga a 2, kutalika kwa telomere kumakhala kufupikitsa, ndipo ntchito ya telomerase ndiyotsika kuposa mwa anthu athanzi. Makhalidwe azomwe amapanga thupi posintha kutalika kwa ma telomeres sanawululidwe.

2. Mulingo wa MDA kwa odwala omwe ali ndi matenda ashuga a 2 komanso anthu athanzi ali ofanana. Matenda opatsirana amatchulidwa kwambiri kwa odwala omwe ali ndi matenda amtundu wa 2 kuposa anthu athanzi lofanana. Kutupa kosafunikira kumakhala ndi gawo lalikulu pakufupikitsa telomeres ndikuwonjezera ntchito ya telomerase.

3. Odwala omwe ali ndi T2DM ndi ma telomeres atali, kuleza kwa kupsinjika kwa oxidative komanso kutupa kosasintha sikumasiyana ndi magawo omwe amagwirizana ndi anthu athanzi

4. Kwa odwala omwe ali ndi T2DM, ma telomeres "achidule" amagwirizanitsidwa ndi kuyendetsa bwino matenda a shuga komanso kupweteka kwambiri pakhungu.

5. Ma telomeres amtundu wautali amateteza odwala omwe ali ndi matenda ashuga pazowonongeka za oxidative nkhawa komanso kutupa kosalekeza.

Palibe kusamvana kwa chidwi.

Kafukufukuyu adachitika ngati gawo la ntchito ya Boma "Kafukufuku wopanga ma atulossiasis kuti apange njira zodziwitsira matenda a atherosclerosis oyambira ngati njira yofunika kwambiri yopangira matenda amtima ndi zovuta zawo."

Lingaliro lakapangidwe ndi kapangidwe - E.N. Dudinskaya, O.N. Tkacheva, I.D. Strazhesko, E.V. Akasheva.

Kutola ndi kukonza zinthu - N.V. Brailova, E.V. Plohova, V.S. Pihtina.

Kusanthula kwa Statistical - V.A. Zopindulitsa.

Kulembalemba - N.V. Brailova.

Kusintha - E.N. Dudinskaya, O.N. Tkacheva, M.V. Shestakova, S.A. Omenyera nkhondo.

Gulu la olemba zikomo A.S. Kruglikov, I.N. Ozerov, N.V. Gomyranova (Federal State Budgetary Institution "State Research Center for Preventive Medicine" ya Ministry of Health of the Russian Federation) ndi D.A. Skvortsov (Institute of Physical and Chemical Biology dzina lake AN Belozersky GBOU VPO MSU dzina lake MV Lomonosov) kuti athandizidwe kuchititsa phunziroli.

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