Department of Cardiology, the First Affiliated Hospital of Soochow University, Suzhou, China.
J Cardiovasc Pharmacol. 2013 May;61(5):416-22. doi: 10.1097/FJC.0b013e318287d501.
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.
我们检验了这样一个假说，即缺血后处理（IPost）会诱导自噬，而自噬的激活有助于保护心脏免受缺血/再灌注损伤。大鼠在 30 分钟缺血后，通过 3 个循环的 10 秒再灌注和 10 秒缺血来实现 IPost。在心室组织再灌注 120 分钟后，通过形态学和生化检查来评估自噬的激活情况。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。结果发现，IPost 增加了自噬小体的形成，LC3-II、Beclin1、溶酶体相关膜蛋白 2 和组织蛋白酶 D 的自噬相关蛋白水平，以及 LC3 和 Beclin1 的 mRNA 水平在预处理心脏的危险区。此外，3-MA 处理显著逆转了 IPost 对梗死面积的减少作用，同时抑制了 LC3 和 Beclin1 的诱导。此外，3-MA 处理抑制了抗凋亡相关蛋白 Bcl-2 的水平，并增加了凋亡相关蛋白 Bad 的水平。综上所述，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。
