Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis
Remote Ischemic Postconditioning Alleviates Cerebral Ischemic Injury by Attenuating Endoplasmic Reticulum Stress-Mediated Apoptosis
复制标题
远程缺血后处理通过减轻内质网应激介导的细胞凋亡来减轻脑缺血损伤
DOI：
10.1007/s12975-014-0359-5
复制
发表时间：
2014-12-01
影响因子：
6.9
通讯作者：
Ji, Xunming
中科院分区：
文献类型：
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作者：
Liu, Xiangrong;Zhao, Shangfeng;Ji, Xunming
远程缺血后处理（RIPostC）已被证明可以保护脑免受中风，但确切的机制仍然没有完全理解。在本研究中，我们的目的是研究是否RIPostC减轻脑缺血再灌注损伤，通过减轻内质网（ER）应激反应。CHOP是内质网应激中的一个多功能转录因子，调节凋亡相关基因Bim和Bcl-2的表达。雄性SD大鼠行右侧大脑中动脉闭塞（MCAO）2 h再灌注，缺血后即刻双侧股动脉缺血10 min再灌注10 min，共3个循环。在缺血开始前30分钟将CHOP siRNA（CHOPi）和对照siRNA（Coni）注射到右侧脑室中。RIPostC、CHOPi或RIPostC + CHOPi应用减少了梗死体积，改善了神经功能，并减少了细胞凋亡。RIPostC增加了葡萄糖调节蛋白78（GRP 78）的蛋白水平，降低了磷酸化EIF 2 α、caspase-12和CHOP的蛋白水平。此外，响应于应用RIPostC、CHOPi或RIPostC + CHOPi，CHOP、Bim和切割的半胱天冬酶-3的表达降低，而Bcl-2的表达增加。总之，RIPostC通过减弱ER应激反应诱导的细胞凋亡来保护大鼠缺血再灌注脑损伤。
Remote ischemic postconditioning (RIPostC) has been proved to protect the brain from stroke, but the precise mechanism remains not fully understood. In the present study, we aimed to investigate whether RIPostC attenuates cerebral ischemia-reperfusion injury by abating endoplasmic reticulum (ER) stress response. CHOP, a multifunctional transcription factor in ER stress, regulates the expression of genes related to apoptosis, such as Bim and Bcl-2. Male SD rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion, and RIPostC was induced by three cycles of 10 min ischemia and 10 min reperfusion on bilateral femoral arteries immediately after ischemia. CHOP siRNA (CHOPi) and control siRNA (Coni) were injected into the right lateral ventricle 30 min before the beginning of ischemia. RIPostC, CHOPi, or RIPostC + CHOPi application reduced infarct volume, improved the neurological function, and decreased cell apoptosis. RIPostC increased the protein level of glucose-regulated protein 78 (GRP78) and decreased the protein level of phosphorylated-EIF2α, caspase-12, and CHOP. Furthermore, the expression of CHOP, Bim and cleaved-caspase-3 was decreased, while Bcl-2 expression was increased in response to application of RIPostC, CHOPi, or RIPostC + CHOPi. In sum, RIPostC protects against ischemia-reperfusion brain injury in rats by attenuating ER stress response-induced apoptosis.