Activation of Autophagy in Ischemic Postconditioning Contributes to Cardioprotective Effects Against Ischemia/Reperfusion Injury in Rat Hearts
Activation of Autophagy in Ischemic Postconditioning Contributes to Cardioprotective Effects Against Ischemia/Reperfusion Injury in Rat Hearts
复制标题
缺血后处理中自噬的激活有助于对大鼠心脏缺血/再灌注损伤的心脏保护作用
DOI：
10.1097/fjc.0b013e318287d501
复制
发表时间：
2013-05-01
影响因子：
3
通讯作者：
Yang, Xiangjun
中科院分区：
文献类型：
--
作者：
Wei, Chao;Li, Hongxia;Yang, Xiangjun
摘要：我们验证了缺血后处理诱导自噬的假设，自噬的激活有助于对大鼠心脏缺血/再灌注损伤的心脏保护作用。对大鼠进行通过3个循环的10秒再灌注，然后在30分钟缺血结束时进行10秒缺血建立的IPost。再灌注120分钟后，通过形态学和生化检查评估心室组织中自噬的激活。为了研究自噬对IPost的贡献，用自噬抑制剂3-甲基腺嘌呤（3-MA）预处理大鼠。我们发现，IPost增加了自噬空泡的形成，自噬相关的蛋白水平LC 3-II，Beclin 1，溶酶体相关膜蛋白2，和组织蛋白酶D，以及LC 3和Beclin 1的mRNA水平在后处理心脏的风险区。此外，3-MA处理显著逆转了IPost对梗死体积的减少作用，同时抑制了LC 3和Beclin 1的诱导。此外，3-MA处理抑制了Bcl-2的抗凋亡相关蛋白水平，并增加了Bad的抗凋亡相关蛋白水平。总之，这些结果表明，IPost的保护作用与大鼠心脏中自噬的激活有关。
Abstract: We tested the hypothesis that ischemic postconditioning (IPost) induces autophagy and the activation of autophagy contributes to the cardioprotective effects against ischemia/reperfusion injury in rat hearts. Rats were subjected to IPost established by 3 cycles of 10-second reperfusion followed by 10-second ischemia at the end of 30-minute ischemia. The activation of autophagy was assessed by the morphological and biochemical examinations after 120-minute reperfusion in ventricular tissue. To investigate the contribution of autophagy to IPost, the rats were pretreated with the autophagy inhibitor 3-methyl-adenine (3-MA). We found that IPost increased the formation of autophagic vacuoles, the autophagic-related protein levels of LC3-II, Beclin1, lysosome-associated membrane protein 2, and cathepsin D, and the mRNA level of LC3 and Beclin1 in the risk zone of the postconditioned hearts. Furthermore, 3-MA treatment significantly reversed the reduction effect of IPost on infarct volume, and in the meantime, inhibited the induction of LC3 and Beclin1. In addition, 3-MA treatment inhibited the antiapoptotic-related protein levels of Bcl-2 and increased the apoptotic-related protein levels of Bad. Taken together, these results indicate that the protective effects of IPost are associated with the activation of autophagy in rat hearts.