大鼠MCAO模型中GST、GSH以及超微结构的改变

GST,GSH,and ultrastructural changes in rat MCAO model

目的自由基造成的氧化损伤是卒中后脑损伤的重要原因之一。谷胱甘肽（Glutathione,GSH）,是细胞抵抗氧化应激损伤的重要分子。谷胱甘肽S-转移酶（Glutathione Stransferase,GST）是一组与GSH相关的Ⅱ相酶,与GSH的应用密切相关,而线粒体是细胞内氧化还原反应的重要场所,揭示脑缺血早期不同时间点GST、GSH以及脑细胞内超微结构尤其是线粒体的变化,对阐明脑缺血中自由基造成的氧化损伤机制具有重要的意义。方法本研究在制备大鼠大脑中动脉栓塞（MCAO）模型的基础上,对不同时间点GST蛋白表达、GSH水平以及脑细胞内超微结构的变化进行了观测。结果 MCAO6h后GSH水平出现下降趋势,24~48h后GSH水平明显低于假手术组,GST蛋白表达也明显下降,线粒体出现肿胀、嵴断裂,神经纤维髓鞘结构紊乱,甚至发现部分神经元高尔基体、内质网结构破坏,细胞坏死、液化现象。结论 MCAO早期就已经出现抗氧化能力的下降,表现为线粒体破坏,GSH下降,GST蛋白表达降低。所以缺血性卒中早期提高机体的抗氧化能力以对抗氧化应激会发挥保护神经元、减少脑损伤的作用。

Objective Oxidative damage caused by free radicals is a major reason in the pathogenesis of brain stroke.Glutathione（GSH）is an important component for resistance to oxidative stress.Glutathione S-transferase（GST）family is a group of GSH-related phase Ⅱ enzyme,and associated with GSH application.Mitochondria is an important place for cellular redox reactions.It is very important to reveal GST,GSH and ultrastructure changes of mitochondria at different time points at the early stage after brain stroke.Methods We set up rat middle cerebral artery occlusion（MCAO）model.GST protein,GSH level and ultrastructural changes within the brain were observed.Results We found,the GSH level had a downward trend after MCAO 6 hours,the GSH levels were significantly lower than the sham group after MCAO 24~48 hours,GST protein expression also decreased significantly at this time point.In addition,we found mitochondrial swelling,mitochondrial cristae rupture,fiber myelin structural disorder,and even observed some neurons undergoing Golgi,endoplasmic reticulum and structural damage,necrosis,liquefaction phenomenon.Our findings suggested that decline in antioxidative capacity was developed in the early onset of MCAO with mitochondria damage,GSH decrease,as well as decreased expression of GST protein.Conclusion Increasing antioxidant capacity in the early stage of ischemic stroke to combat oxidative stress may play an important role in protecting neurons and reducing brain damage.