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二甲双胍对器官缺血再灌注损伤保护作用的研究进展
作者:于慧智1  胡春兰1  王净1  李小杉2  胡春晓1 2 
单位:1. 南京医科大学附属无锡人民医院 麻醉科, 江苏 无锡 214023;
2. 南京医科大学附属无锡人民医院 肺移植中心, 江苏 无锡 214023
关键词:二甲双胍 缺血再灌注 综述 
分类号:R649.9;R977.15
出版年·卷·期(页码):2022·41·第三期(447-451)
摘要:

缺血再灌注(ischemia reperfusion,I/R)引起的组织损伤是多种病理改变、疾病发生及死亡的主要原因。导致I/R损伤的潜在机制包括氧化应激/活性氧增加、炎症反应、线粒体功能障碍、细胞死亡和自噬异常等。二甲双胍(metformin,MET)是治疗2型糖尿病的一线药物,其在延缓衰老和抗肿瘤等方面具有保护作用。多项研究表明,MET对心肌、脑、肾、肝、肠和卵巢的I/R损伤也具有保护作用。本文作者通过综述MET对I/R损伤保护作用的机制及临床研究进展,为后续进一步研究MET在预防和治疗I/R损伤方面提供思路。

参考文献:

[1] MOHSIN A A,CHEN Q,QUAN N,et al.Mitochondrial complex Ⅰ inhibition by metformin limits reperfusion injury[J].J Pharmacol Exp Ther,2019,369(2):282-290.
[2] ZHOU G,MYERS R,LI Y,et al.Role of AMP-activated protein kinase in mechanism of metformin action[J].J Clin Invest,2001,108(8):1167-1174.
[3] Practice Committee of American Society for Reproductive Medicine.Multiple gestation associated with infertility therapy:an American Society for Reproductive Medicine Practice Committee opinion[J].Fertil Steril,2012,97(4):825-834.
[4] BARZILAI N,CRANDALL J P,KRITCHEVSKY S B,et al.Metformin as a tool to target aging[J].Cell Metab,2016,23(6):1060-1065.
[5] MAHSA G,SAEEDEH K,MOHAMMAD S S,et al.Metformin modulates oncogenic expression of HOTAIR gene via promoter methylation and reverses epithelial-mesenchymal transition in MDA-MB-231 cells[J/OL].J Cellul Biochem,2020,122(3-4).doi:10.1002/jcb.29867.
[6] LEECH T,CHATTIPAKORN N,CHATTIPAKORN S C.The beneficial roles of metformin on the brain with cerebral ischaemia/reperfusion injury[J].Pharmacol Res,2019,146:104261.
[7] MENG C,MA L,LIU J,et al.Inflation with carbon monoxide in rat donor lung during cold ischemia phase ameliorates graft injury[J].Exp Biol Med(Maywood),2016,241(3):246-254.
[8] LIU R,FANG X,MENG C,et al.Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats[J].Exp Biol Med(Maywood),2015,240(9):1214-1222.
[9] SIMON C,VARA E,GARUTTI I,et al.Modulation of monocyte chemoattractant protein-1 expression by ischaemic preconditioning in a lung autotransplant model[J].Eur J Cardiothorac Surg,2012,41(4):933-939.
[10] CHEN X,LI X,ZHANG W,et al.Activation of AMPK inhibits inflammatory response during hypoxia and reoxygenation through modulating JNK-mediated NF-kappaB pathway[J].Metabolism,2018,83:256-270.
[11] CAHOVA M,PALENICKOVA E,DANKOVA H,et al.Metformin prevents ischemia reperfusion-induced oxidative stress in the fatty liver by attenuation of reactive oxygen species formation[J].Am J Physiol Gastrointest Liver Physiol,2015,309(2):G100-G111.
[12] ASHABI G,KHODAGHOLI F,KHALAJ L,et al.Activation of AMP-activated protein kinase by metformin protects against global cerebral ischemia in male rats:interference of AMPK/PGC-1alpha pathway[J].Metab Brain Dis,2014,29(1):47-58.
[13] WANG X,YANG L,KANG L,et al.Metformin attenuates myocardial ischemia-reperfusion injury via up-regulation of antioxidant enzymes[J].PLoS One,2017,12(8):e182777.
[14] TOPCU A,BALIK G,ATAK M,et al.An investigation of the effects of metformin on ovarian ischemia-reperfusion injury in rats[J].Eur J Pharmacol,2019,865:172790.
[15] ASHABI G,KHALAJ L,KHODAGHOLI F,et al.Pre-treatment with metformin activates Nrf2 antioxidant pathways and inhibits inflammatory responses through induction of AMPK after transient global cerebral ischemia[J].Metab Brain Dis,2015,30(3):747-754.
[16] ABD-ELSAMEEA A A,MOUSTAF A A,MOHAMED A M.Modulation of the oxidative stress by metformin in the cerebrum of rats exposed to global cerebral ischemia and ischemia/reperfusion[J].Eur Rev Med Pharmacol Sci,2014,18(16):2387-2392.
[17] ZHANG J,HUANG L,SHI X,et al.Metformin protects against myocardial ischemia-reperfusion injury and cell pyroptosis via AMPK/NLRP3 inflammasome pathway[J].Aging(Albany NY),2020,12(23):24270-24287.
[18] HUIJINK T M,VENEMA L H,POSMA R A,et al.Metformin preconditioning and postconditioning to reduce ischemia reperfusion injury in an isolated ex vivo rat and porcine kidney normothermic machine perfusion model[J].Clin Transl Sci,2020,14(1):222-230.
[19] KEVIN L G,CAMARA A K,RIESS M L,et al.Ischemic preconditioning alters real-time measure of O2 radicals in intact hearts with ischemia and reperfusion[J].Am J Physiol Heart Circ Physiol,2003,284(2):H566-H574.
[20] GOMEZ L,THIBAULT H,GHARIB A,et al.Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice[J].Am J Physiol Heart Circ Physiol,2007,293(3):H1654-H1661.
[21] WHITTINGTON H J,HALL A R,MCLAUGHLIN C P,et al.Chronic metformin associated cardioprotection against infarction:not just a glucose lowering phenomenon[J].Cardiovasc Drugs Ther,2013,27(1):5-16.
[22] MOHSIN A A,CHEN Q,QUAN N,et al.Mitochondrial complex I inhibition by metformin limits reperfusion injury[J].J Pharmacol Exp Ther,2019,369(2):282-290.
[23] ZHANG Q,WU Y,ZHANG P,et al.Exercise induces mitochondrial biogenesis after brain ischemia in rats[J].Neuroscience,2012,205:10-17.
[24] LUO T,ZENG X,YANG W,et al.Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway[J].Anatol J Cardiol,2019,21(5):261-271.
[25] YEH C H,CHEN T P,WANG Y C,et al.AMP-activated protein kinase activation during cardioplegia-induced hypoxia/reoxygenation injury attenuates cardiomyocytic apoptosis via reduction of endoplasmic reticulum stress[J].Mediators Inflamm,2010,2010:130636.
[26] RAMACHANDRAN R,SARASWATHI M.Postconditioning with metformin attenuates apoptotic events in cardiomyoblasts associated with ischemic reperfusion injury[J].Cardiovasc Ther,2017,35(6):e12279.
[27] DAYANGAN S C,KARACA G,SEMA O Z,et al.What is the protective effect of metformin on rat ovary against ischemia-reperfusion injury?[J].J Obstet Gynaecol Res,2018,44(2):278-285.
[28] WANG Z S,LIU X H,WANG M,et al.Metformin attenuated the inflammation after renal ischemia/reperfusion and suppressed apoptosis of renal tubular epithelial cell in rats[J].Acta Cir Bras,2015,30(9):617-623.
[29] ACCILI D,ARDEN K C.FoxOs at the crossroads of cellular metabolism,differentiation,and transformation[J].Cell,2004,117(4):421-426.
[30] LOI H,BOAL F,TRONCHERE H,et al.Metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction[J].Front Pharmacol,2019,10:154.
[31] LUO T,ZENG X,YANG W,et al.Treatment with metformin prevents myocardial ischemia-reperfusion injury via STEAP4 signaling pathway[J].Anatol J Cardiol,2019,21(5):261-271.
[32] CAO Z,WANG Y,LONG Z,et al.Interaction between autophagy and the NLRP3 inflammasome[J].Acta Biochim Biophys Sin(Shanghai),2019,51(11):1087-1095.
[33] HUANG K Y,QUE J Q,HU Z S,et al.Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury[J].Int J Biol Sci,2020,16(14):2559-2579.
[34] WU S,ZHANG H,CHEN N,et al.Metformin protects cardiomyocytes against oxygen-glucose deprivation injury by promoting autophagic flux through AMPK pathway[J].J Drug Target,2021(5):1-22.
[35] WANG Y,YANG Z,ZHENG G,et al.Metformin promotes autophagy in ischemia/reperfusion myocardium via cytoplasmic AMPKalpha1 and nuclear AMPKalpha2 pathways[J].Life Sci,2019,225:64-71.
[36] JIANG T,YU J T,ZHU X C,et al.Acute metformin preconditioning confers neuroprotection against focal cerebral ischaemia by pre-activation of AMPK-dependent autophagy[J].Br J Pharmacol,2014,171(13):3146-3157.
[37] ZHANG X,YAN H,YUAN Y,et al.Cerebral ischemia-reperfusion-induced autophagy protects against neuronal injury by mitochondrial clearance[J].Autophagy,2013,9(9):1321-1333.
[38] HORSDAL H T,MEHNERT F,RUNGBY J,et al.Type of preadmission antidiabetic treatment and outcome among patients with ischemic stroke:a nationwide follow-up study[J].J Stroke Cerebrovasc Dis,2012,21(8):717-725.
[39] MIMA Y,KUWASHIRO T,YASAKA M,et al.Impact of metformin on the severity and outcomes of acute ischemic stroke in patients with type 2 diabetes mellitus[J].J Stroke Cerebrovasc Dis,2016,25(2):436-446.
[40] LEXIS C P,VAN DER HORST I C,LIPSIC E,et al.Effect of metformin on left ventricular function after acute myocardial infarction in patients without diabetes:the GIPS-III randomized clinical trial[J].JAMA,2014,311(15):1526-1535.
[41] BASNET S,KOZIKOWSKI A,MAKARYUS A N,et al.Metformin and myocardial injury in patients with diabetes and ST-segment elevation myocardial infarction:a propensity score matched analysis[J].J Am Heart Assoc,2015,4(10):e2314.

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