AKT/GSK3ß-Dependent Autophagy Contributes to the Neuroprotection of Limb Remote Ischemic Postconditioning in the Transient Cerebral Ischemic Rat Model
AKT/GSK3ß-Dependent Autophagy Contributes to the Neuroprotection of Limb Remote Ischemic Postconditioning in the Transient Cerebral Ischemic Rat Model
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DOI：
10.1111/cns.12016
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发表时间：
2012-12-01
影响因子：
5.5
通讯作者：
Ji, Xun-Ming
中科院分区：
文献类型：
--
作者：
Qi, Zhi-Feng;Luo, Yu-Min;Ji, Xun-Ming
背景肢体缺血后处理（RIPostC）是一种有效的脑缺血保护策略。然而，肢体RIPostC应用的时间窗和RIPostC背后的机制仍不清楚。目的：在这项研究中，我们研究了保护效果和自噬在肢体RIPostC使用短暂的大脑中动脉闭塞大鼠模型的作用。结果再灌注早期应用肢体RIPostC可缩小梗死范围，改善神经功能。在肢体RIPostC大鼠的神经元中，半暗带组织中的自噬水平升高，AKT和糖原合成酶激酶3 β（GSK 3 β）的磷酸化增加。在肢体RIPostC之前通过AKT抑制剂LY 294002阻断AKT/GSK 3 β途径抑制RIPostC诱导的自噬，并导致RIPostC大鼠中caspase-3的激活，这表明AKT/GSK 3 β依赖性自噬在减少脑缺血后细胞死亡中的关键作用。结论这些结果有助于优化RIPostC使用的时间窗，并提供新的见解，更好地理解肢体RIPostC中自噬的保护机制。
Background Limb remote ischemic postconditioning (RIPostC) has been recognized as an applicable strategy in protecting against cerebral ischemic injury. However, the time window for application of limb RIPostC and the mechanisms behind RIPostC are still unclear. Aims In this study, we investigated the protective efficacy and the role of autophagy in limb RIPostC using a transient middle cerebral artery occlusion rat model. Results Limb RIPostC applied in the early phase of reperfusion reduced infarct size and improved neurological function. Autophagy levels in penumbral tissues were elevated in neurons of limb RIPostC rats, with an increase in the phosphorylation of AKT and glycogen synthase kinase 3 beta (GSK3 beta). Blocking the AKT/GSK3 beta pathway via the AKT inhibitor LY294002 prior to limb RIPostC suppressed the RIPostC-induced autophagy and resulted in the activation of caspase-3 in RIPostC rats, suggesting a critical role for AKT/GSK3 beta-dependent autophagy in reducing cell death after cerebral ischemia. Conclusions These results aid optimization of the time window for RIPostC use and offer novel insight into, and a better understanding of, the protective mechanism of autophagy in limb RIPostC.