Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress
Adiponectin cardioprotection after myocardial ischemia/reperfusion involves the reduction of oxidative/nitrative stress
复制标题
心肌缺血/再灌注后脂联素的心脏保护作用涉及减少氧化/硝化应激
DOI：
10.1161/circulationaha.106.666941
复制
发表时间：
2007-03-20
期刊：
影响因子：
37.8
通讯作者：
Ma, Xin L.
中科院分区：
文献类型：
--
作者：
Tao, Ling;Gao, Erhe;Ma, Xin L.
背景-多项临床研究表明，2型糖尿病患者的脂联素水平显着降低，并且脂联素水平与心肌缺血的风险呈负相关。本研究的目的是确定脂联素发挥其对心肌缺血/reperfusion.Methods和结果的保护作用的机制脂联素（-/-）或野生型小鼠进行30分钟的心肌缺血，随后3小时或24小时（梗死面积和心脏功能）的再灌注。比较心肌梗死面积和细胞凋亡，过氧亚硝酸盐，一氧化氮（NO）和超氧化物的产生，诱导型NO合酶（iNOS）和gp 91（phox）蛋白表达。脂联素（-/-）小鼠心肌细胞凋亡和梗死面积明显增加（P < 0.01）。与野生型小鼠相比，脂联素（-/-）小鼠心肌组织中NO、超氧化物及其细胞毒性反应产物过氧亚硝酸盐的生成均显著增加（P < 0.01）。此外，心肌缺血/再灌注诱导的iNOS和gp 91 phox蛋白表达进一步增强，但内皮NOS磷酸化减少，从脂联素（-/-）小鼠的心脏组织。在再灌注前10分钟给予脂联素球状结构域可减少心肌缺血/再灌注诱导的iNOS/gp 91（phox）蛋白表达，减少NO/超氧化物的产生，阻断过氧亚硝酸盐的形成，在脂联素（-/-）小鼠中观察到的促凋亡和梗死扩大效应。结论-本研究表明脂联素是一种保护心脏免受缺血/再灌注损伤的天然分子。通过抑制iNOS和烟酰胺腺嘌呤二核苷酸磷酸氧化酶蛋白的表达以及由此产生的氧化/硝化应激而引起的再灌注损伤。
Background-Several clinical studies have demonstrated that levels of adiponectin are significantly reduced in patients with type 2 diabetes and that adiponectin levels are inversely related to the risk of myocardial ischemia. The present study was designed to determine the mechanism by which adiponectin exerts its protective effects against myocardial ischemia/reperfusion.Methods and Results-Adiponectin(-/-) or wild-type mice were subjected to 30 minutes of myocardial ischemia followed by 3 hours or 24 hours (infarct size and cardiac function) of reperfusion. Myocardial infarct size and apoptosis, production of peroxynitrite, nitric oxide (NO) and superoxide, and inducible NO synthase (iNOS) and gp91(phox) protein expression were compared. Myocardial apoptosis and infarct size were markedly enhanced in adiponectin(-/-) mice (P < 0.01). Formation of NO, superoxide, and their cytotoxic reaction product, peroxynitrite, were all significantly higher in cardiac tissue obtained from adiponectin(-/-) than from wild-type mice (P < 0.01). Moreover, myocardial ischemia/reperfusion-induced iNOS and gp91phox protein expression was further enhanced, but endothelial NOS phosphorylation was reduced in cardiac tissue from adiponectin (-/-) mice. Administration of the globular domain of adiponectin 10 minutes before reperfusion reduced myocardial ischemia/reperfusion-induced iNOS/gp91(phox) protein expression, decreased NO/superoxide production, blocked peroxynitrite formation, and reversed proapoptotic and infarct-enlargement effects observed in adiponectin(-/-) mice.Conclusion-The present study demonstrates that adiponectin is a natural molecule that protects hearts from ischemia/ reperfusion injury by inhibition of iNOS and nicotinamide adenine dinucleotide phosphate-oxidase protein expression and resultant oxidative/nitrative stress.