依达拉奉在大鼠局灶性脑缺血细胞中对Drp1和Mfn2动态变化的影响

Effect of Edaravone on the Dynamic Change of Drp1 and Mfn2 in Rats with Focal Cerebral Ischemia

目的探讨依达拉奉在大鼠局灶性脑缺血细胞中对Drp1及Mfn2动态变化的影响及其保护机制。方法采用线栓法建立大脑中动脉缺血模型,并将72只大鼠采用数字表法随机分为假手术组、脑缺血组、依达拉奉组,每组又根据时间的不同分为1、3、7天3个不同亚组。HE染色观察大脑皮质神经元形态结构,Western blot法检测Drp1及Mfn2的蛋白含量,RT-PCR检测Drp1及Mfn2m RNA基因的表达情况。结果脑缺血组的Drp1蛋白表达量明显高于假手术组及依达拉奉组(P<0.05),在第1、3、7天中的表达呈递增的趋势,给予依达拉奉治疗后,可以下调Drp1蛋白的表达,差异有统计学意义(P<0.05);脑缺血组的Mfn2蛋白表达量明显低于假手术组及依达拉奉组(P<0.05),在第1、3、7天中的表达呈递减的趋势,给予依达拉奉治疗后可上调Mfn2蛋白的表达,差异有统计学意义(P<0.05)。RT-PCR表达结果与Western blot法检验结果一致。结论依达拉奉治疗大鼠脑缺血可能与依达拉奉减少氧自由基生成、维持线粒体动态平衡使Drp1表达减少,Mfn2表达增多有关,从而发挥神经保护作用。

Objective To study the the effect of edaravone to dynamic change of Drp1and Mfn2 in focal cerebral ischemia rats and protective mechanisms of ischemic brain cells it. Methods Using line plug method to establish MCAO, and according to random number table method 72 rats were divided into control group, ischemic group and Ed group.According to time,they wore divided into three subgroups 1d,3d,7d. HE staining to observe the cerebral cortex neuron morphological structure, western blot test way used to obserre Drp1 and the protein content of Mfn2, RT-PCR way used to obserre Drp1 and Mfn2＇S mRNA expression. Results Drp1 protein expression of cerebral ischemia group were significantly higher than the Sham group and Ed group （P〈0.05）, and the 1d, 3d, 7d expression were in increasing trend.The edaravone treatment can decrease the expression of Drp1（P〈0.05）. Mfn2 protein expression of cerebral ischemia group were significantly lower than the control group and in accordance with the adr group （P〈0.05）, and the 1d, 3d, 7d expression were in decreasing trend.The edaravone treatment can increase the expression of Mfn2（P〈0.05）, and the difference was statistically significant. The results of RT-PCR and western blot were the same. Conclusion The edaravone in treatment of ischemia rats may be related to the edaravone in reducing ROS generation and maintaining mitochondrial dynamic balance to reduce Drp1 expression and increase Mfn2 expression of, Mfn2 expression, thus to play a neuroprotective function.