Propofol prevents neuronal mtDNA deletion and cerebral damage due to ischemia/reperfusion injury in rats
Propofol prevents neuronal mtDNA deletion and cerebral damage due to ischemia/reperfusion injury in rats
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DOI：
10.1016/j.brainres.2014.10.016
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发表时间：
2015-01
期刊：
影响因子：
2.9
通讯作者：
Zi-yong Yue;Hong Dong;Ya-fang Wang;Yuhong Liu;Chun-yu Song;Wan-chao Yang;H. Qian;Shu-jun Lu;Fei-fei Chang
中科院分区：
文献类型：
--
作者：
Zi-yong Yue;Hong Dong;Ya-fang Wang;Yuhong Liu;Chun-yu Song;Wan-chao Yang;H. Qian;Shu-jun Lu;Fei-fei Chang
异丙酚是一种常用的静脉麻醉药，已被证明对脑缺血再灌注（I/R）损伤具有神经保护作用。目前尚不清楚这种保护作用是否与防止神经元线粒体脱氧核糖核酸（mtDNA）缺失有关。81只Wistar大鼠随机分为假手术组（S组）、缺血再灌注组（I/R组）和异丙酚组（P组）。夹闭双侧颈总动脉10 min，造成脑缺血。聚合酶链反应（PCR）检测线粒体DNA缺失。酶标仪检测线粒体膜电位（MMP）变化。电镜观察神经元超微结构。I/R后MMP显著降低（P<0.05）。脑I/R损伤时神经元线粒体超微结构严重受损。与I/R组相比，诱导I/R前1h静脉注射丙泊酚（1.0mg/kg/min），缺血/再灌注损伤后神经元结构和MMP得到较好的保护，线粒体DNA缺失减少（P<0.05）。这些数据表明，异丙酚防止线粒体DNA缺失，并保持正常的结构和MMP，这是重要的正常线粒体功能和增加神经元抵抗I/R损伤。
Propofol is a commonly used intravenous anesthetic that has been demonstrated to be neuroprotective against cerebral ischemia–reperfusion (I/R) injury. It remains unclear whether this protective effect has any relationship with the prevention of neuronal mitochondrial deoxyribonucleic acid (mtDNA) deletion. In this study, 81 Wistar rats were randomly divided into three groups (n=27 each): sham (Sgroup), ischemia/reperfusion (I/Rgroup), or propofol (Pgroup). Cerebral ischemia was induced by clamping the bilateral common carotid arteries for 10 min. A polymerase chain reaction (PCR) was conducted to determine mtDNA deletion. The mitochondrial membrane potential (MMP) changes were detected via microplate reader. The neuronal ultrastructure was visualized via electron microscope. MMP significantly decreased afterI/R(P<0.05 compared with theSgroup). Severe damage to the ultrastructure of neuronal mitochondria was observed in cerebralI/Rinjury. When propofol (1.0 mg/kg/min) was administered intravenously for 1 h prior to the induction ofI/R, the neuronal structure and MMP were well preserved, and mtDNA deletion was reduced after ischemia/reperfusion injury compared with theI/Rgroup (P<0.05). These data suggested that propofol prevented mtDNA deletion and preserved a normal structure and MMP, which are important for normal mitochondrial function and increase neuronal resistance toI/Rinjury.