Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage
Icariin protects cardiomyocytes against ischaemia/reperfusion injury by attenuating sirtuin 1-dependent mitochondrial oxidative damage
复制标题
淫羊藿苷通过减弱 Sirtuin 1 依赖性线粒体氧化损伤，保护心肌细胞免受缺血/再灌注损伤
DOI：
10.1111/bph.14457
复制
发表时间：
2018-11-01
影响因子：
7.3
通讯作者：
Ha, Xiao-qin
中科院分区：
文献类型：
--
作者：
Wu, Bing;Feng, Jian-yu;Ha, Xiao-qin
研究背景与目的：淫羊藿苷是传统中药的主要活性成分，因其独特的抗缺血性心脏病的药理作用而受到越来越多的关注。组蛋白去乙酰化酶sirtuin-1在缺血再灌注（I/R）损伤中起保护作用，本研究旨在探讨淫羊藿苷在心脏I/R损伤模型中的保护作用，并阐明sirtuin-1可能参与的机制。实验方法在体内（小鼠心脏）、离体（离体大鼠心脏）和体外（新生大鼠心肌细胞和H9 c2细胞）模拟I/R损伤。在I/R损伤之前，动物或细胞暴露于淫羊藿苷，有或没有sirtuin-1的抑制剂（sirtinol和SIRT 1 siRNA）。关键词在体内和体外，在I/R之前给予淫羊藿苷显著改善I/R后心脏收缩，并限制梗死面积和肌酸激酶MB和LDH从受损心肌的渗漏。淫羊藿苷还减弱I/R诱导的线粒体氧化损伤，降低丙二醛含量，增加超氧化物歧化酶活性和锰超氧化物歧化酶的表达。淫羊藿苷通过提高线粒体膜电位和细胞色素C稳定性，显著改善线粒体膜稳态，从而进一步抑制细胞凋亡。Sirtuin-1在用淫羊藿苷处理的心脏中显著上调，而Ac-FOXO 1同时下调。重要的是，sirtinol和SIRT 1 siRNA无论是阻断淫羊藿苷诱导的心脏保护或破坏淫羊藿苷介导的线粒体homeostasis.CONCLUSIONS AND IMPLICATIONsPretreatment与淫羊藿苷保护心肌细胞I/R诱导的氧化应激通过激活sirtuin-1 /FOXO 1信号。
BACKGROUND AND PURPOSEIcariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1.EXPERIMENTAL APPROACHI/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA).KEY RESULTSIn vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis.CONCLUSIONS AND IMPLICATIONSPretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.