Myocardial autophagy variation during acute myocardial infarction in rats: the effects of carvedilol
Myocardial autophagy variation during acute myocardial infarction in rats: the effects of carvedilol
复制标题
DOI：
10.3760/cma.j.issn.0366-6999.2009.19.033
复制
发表时间：
2009-10-05
影响因子：
6.1
通讯作者：
Wu Xue-si
中科院分区：
文献类型：
--
作者：
Zhang Jing-lan;Lu Jia-kai;Wu Xue-si
背景心肌细胞丢失是急性心肌梗死（AMI）相关性心力衰竭的机制之一。自噬是真核生物细胞中常见的生物学过程。AMI后心肌细胞丢失与自噬的关系尚不清楚。卡维地洛是一种非选择性α 1和β受体阻滞剂，也能抑制缺血引起的心肌细胞坏死和凋亡。然而，卡维地洛的治疗效果和自噬之间的关联仍然没有得到很好的理解。本研究旨在建立大鼠急性心肌梗死（AMI）模型，观察AMI大鼠心肌不同区域自噬的变化及卡维地洛对其的影响。方法将动物随机分为假手术组、AMI组、氯喹干预组和卡维地洛组。结扎大鼠冠状动脉左前降支建立急性心肌梗死模型。分别于AMI组结扎后40 min、2 h、24 h、2周、氯喹干预组结扎后40 min、其他各组结扎后2周取心。电镜下观察到心肌细胞内存在自噬空泡。采用免疫组化和Western blotting方法检测心肌组织中自噬、抗凋亡和凋亡相关蛋白MAPLC-3、Beclin-1、Bcl-xl和Bax的表达。在与梗死相邻的区域发现了大量AV。与梗死区和正常区相比，梗死边缘区AV的形成明显增加（P
Background The loss of cardiac myocytes is one of the mechanisms involved in acute myocardial infarction (AMI)-related heart failure. Autophagy is a common biological process in eukaryote cells. The relationship between cardiac myocyte loss and autophagy after AMI is still unclear. Carvedilol, a non-selective alpha 1- and beta-receptor blocker, also suppresses cardiac myocyte necrosis and apoptosis induced by ischemia. However, the association between the therapeutic effects of carvedilol and autophagy is still not well understood. The aim of the present study was to establish a rat model of AMI and observe changes in autophagy in different zones of the myocardium and the effects of carvedilol on autophagy in AMI rats.Methods The animals were randomly assigned to a sham group, an AMI group, a chloroquine intervention group and a carvedilol group. The AMI rat model was established by ligating the left anterior descending coronary artery. The hearts were harvested at 40 minutes, 2 hours, 24 hours and 2 weeks after ligation in the AMI group, at 40 minutes in the chloroquine intervention group and at 2 weeks in other groups. Presence of autophagic vacuoles (AV) in the myocytes was observed by electron microscopy. The expression of autophagy-, anti-apoptotic- and apoptotic-related proteins, MAPLC-3, Beclin-1, Bcl-xl and Bax, were detected by immunohistochemical staining and Western blotting.Results AVs were not observed in necrotic regions of the myocardium 40 minutes after ligation of the coronary artery. A large number of AVs were found in the region bordering the infarction. Compared with the infarction region and the normal region, the formation of AV was significantly increased in the region bordering the infarction (P