上海交通大学学报（医学版）

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2021 , Vol. 41 >Issue 6: 826 - 829

DOI: https://doi.org/10.3969/j.issn.1674-8115.2021.06.021

综述

活性氧介导心肌缺血再灌注损伤的研究进展

  • 韦亚忠 ,
  • 薛晓梅 ,
  • 何斌
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  • 上海交通大学附属胸科医院重症医学科，上海 200092
韦亚忠（1995—），男，硕士生；电子信箱：weiyazhong@sjtu.edu.cn。

网络出版日期: 2021-06-29

基金资助

国家自然科学基金(82072199);上海申康医院发展中心第二轮临床三年行动计划(SHDC2020CR3084B)

收起

Research progress in myocardial ischemia-reperfusion injury mediated by mitochondrial reactive oxygen species

  • Ya-zhong WEI ,
  • Xiao-mei XUE ,
  • Bin HE
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  • Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200092, China

Online published: 2021-06-29

Supported by

National Natural Science Foundation of China(82072199);Clinical Research Plan of Shanghai Hospital Development Center(SHDC2020CR3084B)

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摘要

经皮冠状动脉介入治疗技术广泛开展，使得急性心肌梗死得到有效治疗，但由此引发的心肌缺血再灌注损伤（myocardial ischemia-reperfusion injury，MIRI）却严重影响着患者的预后。在急性心肌梗死的缺血再灌注期，氧化应激反应可严重损害心脏功能。过量的线粒体活性氧（mitochondrial reactive oxygen species，mtROS）可影响线粒体的通透性，造成其内部特定分子的氧化损伤，是导致MIRI的主要驱动因素。同时，mtROS还可以促进心肌梗死后的炎症信号转导、调控心肌细胞凋亡并参与心肌梗死后的心肌重塑。该文就心肌梗死缺血再灌注期mtROS的产生机制及降低mtROS在心肌梗死治疗中的临床价值与应用前景进行综述。

关键词： 心肌缺血再灌注损伤; 线粒体; 活性氧

本文引用格式

韦亚忠 , 薛晓梅 , 何斌 . 活性氧介导心肌缺血再灌注损伤的研究进展[J]. 上海交通大学学报（医学版）, 2021 , 41(6) : 826 -829 . DOI: 10.3969/j.issn.1674-8115.2021.06.021

Abstract

With the development of percutaneous coronary intervention technology, acute myocardial infarction has been effectively treated, but the myocardial ischemia-reperfusion injury (MIRI) has seriously affected the prognosis of patients. During the ischemia-reperfusion period of acute myocardial infarction, oxidative stress can seriously damage cardiac function. Excessive mitochondrial reactive oxygen species (mtROS) can affect mitochondrial permeability, and cause oxidative damage of specific molecules inside the mitochondria, which is the main driving factor for MIRI. In addition, mtROS can promote the signal transduction of inflammatory after myocardial infarction, regulate myocardial cell apoptosis, and participate in myocardial remodeling after myocardial infarction. This article reviews the mechanism of mtROS production in MIRI period and the clinical value and application prospect of reducing mtROS in the treatment of myocardial infarction.

Key words： myocardial ischemia-reperfusion injury (MIRI); mitochondria; reactive oxygen species (ROS)

参考文献

1 Prabhu SD, Frangogiannis NG. The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis[J]. Circ Res, 2016, 119(1): 91-112.
2 Maeda H, Kami D, Maeda R, et al. TAT-dextran-mediated mitochondrial transfer enhances recovery from models of reperfusion injury in cultured cardiomyocytes[J]. J Cell Mol Med, 2020, 24(9): 5007-5020.
3 Chouchani ET, Pell VR, Gaude E, et al. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS[J]. Nature, 2014, 515(7527): 431-435.
4 Kasai, Shimizu S, Tatara Y, et al. Regulation of Nrf2 by mitochondrial reactive oxygen species in physiology and pathology[J]. Biomolecules, 2020, 10(2): E320.
5 Bertero E, Maack C. Calcium signaling and reactive oxygen species in mitochondria[J]. Circ Res, 2018, 122(10): 1460-1478.
6 Giorgio M, Migliaccio E, Orsini F, et al. Electron transfer between cytochrome c and P66SHC generates reactive oxygen species that trigger mitochondrial apoptosis[J]. Cell, 2005, 122(2): 221-233.
7 Boengler K, Bornbaum J, Schlüter KD, et al. P66SHC and its role in ischemic cardiovascular diseases[J]. Basic Res Cardiol, 2019, 114(4): 29.
8 Xiao YJ, Xia JJ, Cheng JQ, et al. Inhibition of S-adenosylhomocysteine hydrolase induces endothelial dysfunction via epigenetic regulation of P66SHC-mediated oxidative stress pathway[J]. Circulation, 2019, 139(19): 2260-2277.
9 Wang JN, Yang Q, Yang C, et al. Smad3 promotes AKI sensitivity in diabetic mice via interaction with p53 and induction of NOX4-dependent ROS production[J]. Redox Biol, 2020, 32: 101479.
10 Matsushima S, Kuroda J, Ago T, et al. Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α[J]. Circ Res, 2013, 112(8): 1135-1149.
11 Zhang YX, Murugesan P, Huang K, et al. NADPH oxidases and oxidase crosstalk in cardiovascular diseases: novel therapeutic targets[J]. Nat Rev Cardiol, 2020, 17(3): 170-194.
12 Siu KL, Lotz C, Ping P, et al. Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS[J]. J Mol Cell Cardiol, 2015, 78: 174-185.
13 Jannetti SA, Zeglis BM, Zalutsky MR, et al. Poly(ADP-ribose)polymerase (PARP) inhibitors and radiation therapy[J]. Front Pharmacol, 2020, 11: 170.
14 Hocsak E, Szabo V, Kalman N, et al. PARP inhibition protects mitochondria and reduces ROS production via PARP-1-ATF4-MKP-1-MAPK retrograde pathway[J]. Free Radic Biol Med, 2017, 108: 770-784.
15 Di Lisa F, Carpi A, Giorgio V, et al. The mitochondrial permeability transition pore and cyclophilin D in cardioprotection[J]. Biochim Biophys Acta, 2011, 1813(7): 1316-1322.
16 Cadenas S. ROS and redox signaling in myocardial ischemia-reperfusion injury and cardioprotection[J]. Free Radic Biol Med, 2018, 117: 76-89.
17 Shimizu Y, Lambert JP, Nicholson CK, et al. DJ-1 protects the heart against ischemia-reperfusion injury by regulating mitochondrial fission[J]. J Mol Cell Cardiol, 2016, 97: 56-66.
18 Akbulut A, Keseroglu BB, Koca G, et al. Scintigraphic evaluation of renoprotective effects of coenzyme Q10 in a rat renal ischemia-reperfusion injury[J]. Nucl Med Commun, 2019, 40(10): 1011-1021.
19 Khan A, Johnson DK, Carlson S, et al. NT-pro BNP predicts myocardial injury post-vascular surgery and is reduced with CoQ10: a randomized double-blind trial[J]. Ann Vasc Surg, 2020, 64: 292-302.
20 Adlam VJ, Harrison JC, Porteous CM, et al. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury[J]. FASEB J, 2005, 19(9): 1088-1095.
21 Machiraju P, Wang X, Sabouny R, et al. SS-31 peptide reverses the mitochondrial fragmentation present in fibroblasts from patients with DCMA, a mitochondrial cardiomyopathy[J]. Front Cardiovasc Med, 2019, 6: 167.
22 Cho J, Won K, Wu D, et al. Potent mitochondria-targeted peptides reduce myocardial infarction in rats[J]. Coron Artery Dis, 2007, 18(3): 215-220.
23 Cung TT, Morel O, Cayla G, et al. Cyclosporine before PCI in patients with acute myocardial infarction[J]. N Engl J Med, 2015, 373(11): 1021-1031.
24 Wang M, Liu S, Wang H, et al. Morphine post-conditioning-induced up-regulation of lncRNA TINCR protects cardiomyocytes from ischemia-reperfusion injury via inhibiting degradation and ubiquitination of FGF1[J]. QJM, 2020, 113(12): 859-869.
25 Zi C, Zhang C, Yang Y, et al. Penehyclidine hydrochloride protects against anoxia/reoxygenation injury in cardiomyocytes through ATP-sensitive potassium channels, and the Akt/GSK-3β and Akt/mTOR signaling pathways[J]. Cell Biol Int, 2020, 44(6): 1353-1362.
26 Mao ZJ, Lin H, Hou JW, et al. A meta-analysis of resveratrol protects against myocardial ischemia/reperfusion injury: evidence from small animal studies and insight into molecular mechanisms[J]. Oxid Med Cell Longev, 2019, 2019: 5793867.
27 Dyck G, Raj P, Zieroth S, et al. The effects of resveratrol in patients with cardiovascular disease and heart failure: a narrative review[J]. Int J Mol Sci, 2019, 20(4): 904.
28 Yamamoto T, Byun J, Zhai P, et al. Nicotinamide mononucleotide, an intermediate of NAD+ synthesis, protects the heart from ischemia and reperfusion[J]. PLoS One, 2014, 9(6): e98972.
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