Induction of autophagy contributes to the myocardial protection of valsartan against ischemia-reperfusion injury
Induction of autophagy contributes to the myocardial protection of valsartan against ischemia-reperfusion injury
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DOI：
10.3892/mmr.2013.1708
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发表时间：
2013-12-01
影响因子：
3.4
通讯作者：
Luo, Jiandong
中科院分区：
文献类型：
--
作者：
Wu, Xiaoqian;He, Lishan;Luo, Jiandong
缬沙坦对缺血/再灌注（I/R）损伤的心肌保护作用机制复杂且尚不清楚。本研究的目的是探讨自噬机制是否参与了对缬沙坦诱导的I/R损伤的保护作用。在体内大鼠心脏进行缺血30分钟结扎左冠状动脉前降支，然后再灌注120分钟。3-自噬螯合作用的特异性抑制剂甲基腺嘌呤（3-MA）被用来抑制自噬。测定血流动力学、心肌梗死面积及LC 3B蛋白。Western blot分析缬沙坦诱导自噬的机制。缬沙坦预处理可显著缩小心肌梗死面积并诱导心肌细胞自噬。血流动力学检测显示3-MA可减弱缬沙坦诱导的心功能恢复。与此相反，3-MA减少缬沙坦诱导的改善对大鼠心脏I/R损伤的组织学和梗死。缬沙坦预处理通过AKT/mTOR/S6 K途径诱导自噬，独立于Beclin 1。结论：缬沙坦预处理通过AKT/mTOR/S6 K通路诱导自噬，对缺血再灌注损伤心肌具有保护作用。
The mechanisms underlying the myocardial protection of valsartan against ischemia/reperfusion (I/R) injury are complicated and remain unclear. The aim of this study was to investigate whether autophagy machinery was involved in the protection against I/R injury that is induced by valsartan. In vivo rat hearts were subjected to ischemia by 30 min ligation of the left anterior descending coronary artery, followed by a 120 min reperfusion. 3-methyladenine (3-MA), a specific inhibitor on autophagic sequestration, was used to inhibit autophagy. The hemodynamics, infarct size of the ventricle and LC3B protein were measured. Western blot analysis was performed to investigate the mechanism by which autophagy was induced by valsartan. Valsartan preconditioning resulted in a significant decrease in infarct size and induced autophagy in the rat heart subjected to I/R injury. The hemodynamics assay showed that the valsartan-induced cardiac functional recovery was attenuated by 3-MA. By contrast, 3-MA decreased the improvement induced by valsartan on the histology and infarction of the rat heart subjected to I/R injury. Valsartan preconditioning induced autophagy via the AKT/mTOR/S6K pathway, independent of Beclin1. In conclusion, valsartan preconditioning induced autophagy via the AKT/mTOR/S6K pathway, which contributed to the myocardial protection against I/R injury.