Protective effects of propofol against whole cerebral ischemia/reperfusion injury in rats through the inhibition of the apoptosis-inducing factor pathway
Protective effects of propofol against whole cerebral ischemia/reperfusion injury in rats through the inhibition of the apoptosis-inducing factor pathway
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DOI：
10.1016/j.brainres.2016.05.006
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发表时间：
2016-08-01
期刊：
影响因子：
2.9
通讯作者：
Qian, Hua
中科院分区：
文献类型：
--
作者：
Tao, Tao;Li, Chun-lei;Qian, Hua
脑缺血/再灌注损伤可引起神经细胞凋亡，凋亡的发生与信号转导通路有关。细胞色素c从线粒体中释放，随后caspase 9和caspase 3的激活是重要的步骤。目前，一种新的线粒体蛋白--凋亡诱导因子（AIF）已被证实与非半胱天冬酶依赖的凋亡途径有关。本研究旨在探讨丙泊酚通过抑制AIF介导的全脑I/R损伤诱导的细胞凋亡对脑缺血再灌注损伤的保护作用。120只经哈尔滨医科大学动物管理委员会批准的Wistar大鼠随机分为假手术组（S组）、脑缺血再灌注损伤组（I/R组）和异丙酚治疗组（P组）。P组在诱导缺血前1h静脉注射异丙酚（1.0mg/kg/min）。再灌注24 h后，流式细胞仪检测三组细胞凋亡率。酶标仪检测线粒体膜电位（MMP）变化。分别于再灌注6 h、24 h、48 h，用Western blot检测B细胞白血病2（Bcl-2）、Bcl-2相关X蛋白（Bax）和AIF的表达。我们的研究结果表明，P组细胞凋亡水平低于I/R组，异丙酚可以保护MMP。P组Bcl-2/Bax比值明显高于I/R组。P组AIF由线粒体向核的转位较I/R组明显减少。提示异丙酚对脑缺血再灌注损伤的保护作用可能与抑制AIF从线粒体向细胞核转位有关。(C)2016爱思唯尔B. V.保留所有权利。
Cerebral ischemia/reperfusion (I/R) injury could cause neural apoptosis that involved the signaling cascades. Cytochrome c release from the mitochondria and the followed activation of caspase 9 and caspase 3 are the important steps. Now, a new mitochondrial protein, apoptosis-inducing factor (AIF), has been shown to have relationship with the caspase-independent apoptotic pathway. In this study, we investigated the protective effects of propofol through inhibiting AIF-mediated apoptosis induced by whole cerebral I/R injury in rats. 120 Wistar rats that obtained the permission of the animal care committee of Harbin Medical University were randomly divided into three groups: sham group (S group), cerebral ischemia/reperfusion injury group (I/R group), and propofol treatment group (P group). Propofol (1.0 mg/kg/min) was administered intravenously for 1 h before the induction of ischemia in P group. The apoptotic rate in three groups was detected by flow cytometry after 24 h of reperfusion. The mitochondria] membrane potential (MMP) changes were detected via microplate reader. The expressions of B-cell leukemia-2 (Bcl-2), Bcl-2 associated X protein (Bax) and AIF were evaluated using Western blot after 6 h, 24 h and 48 h of reperfusion. The results of our study showed that apoptotic level was lower in P group compared with I/R group and propofol could protect MMP. The ratio of Bcl-2/Bax was significantly higher in P group compared with I/R group. The translocation of AIF from mitochondrial to nucleus was lower in P group than that in I/R group. Our findings suggested that the protective effects of propofol on cerebral I/R injury might be associated with inhibiting translocation of AIF from mitochondria] to the nucleus in hippocampal neurons. (C) 2016 Elsevier B.V. All rights reserved.