依达拉奉对血管性痴呆大鼠海马线粒体COX活性及基因表达的影响

摘要

Objective To explore the effect of the activity of cytochrome C oxidase (COX) and the expression of COX in the vascular dementia (VD) rats after administrated with edaravone.Methods The VD rat model was established by permanent bilateral occlusion of both common carotid arteries.The rats were divided into 4 groups randomly as control,VD model (0.9% sodium chloride),edaravone (3 mg/kg per day,for 20 d) and duxil groups (gastric perfusion,20 mg/kg per day) after place navigation training.The treatment was from the 7th day after operation and lasted for 20 d.At the 1st and 2nd month the heads of rats were cut down for brain to measure the activity of COX and the change of genetic expression.Results The activity of COX in edaravone and duxil group was higher significantly than that of model group(P＜0.05) in the 1st and 2nd month after operations,the expression of COX in model group decreased than that of edaravone group(P＜0.05) which was similar to duxil group.Edaravone group occurred 3 new mutations of COX, which was 3 less than that of control group.Compared with model group,edaravone group occurred 3 new mutations of COX and lost 3 genetic points.The COX in edaravone group had neither mutable points in model group nor control group.Duxil group had both of the mutable points.Conclusions Edaravone can protect the nerve function through lessening mitochondria oxidative lesion by increasing activity of COX and decreasing gene mutation rate of COX.%目的 探讨依达拉奉对血管性痴呆(VD)大鼠海马组织的细胞色素C氧化酶(COX)活性及基因表达的影响.方法 采用双侧颈总动脉永久结扎法制备慢性前脑缺血大鼠模型,分依达拉奉治疗组(皮下注射,每日1次,3 mg/kg体重),甲磺酸阿米三嗪(都可喜,灌胃,每日1次,20 mg/kg体重)组和模型组,另取正常大鼠为正常对照组.自手术7 d起给药,共20 d后,各组分别取1及2个月为时间点,处死取脑,测定大鼠海马组织COX活性及基因表达并进行基因突变分析.结果 提取各组大鼠海马组织线粒体后,COX活性检测结果显示:术后1、2个月依达拉奉治疗组COX活性明显高于相应时间点模型组(P＜0.05),并有高于都可喜组趋势.依达拉奉治疗组COX表达量高于模型组(P＜0.05),与都可喜组无差异.依达拉奉组COX基因新出现3处基因突变,比正常组少3个突变位点,与模型组比新出现3处基因突变,少3处突变位点.COX基因依达拉奉组没有模型组的突变位点,也没有对照组突变位点,都可喜组突变频率较高既有正常对照组的突变位点,也有模型组的突变位点.结论 依达拉奉可以使VD大鼠海马组织COX活性升高,COX基因突变率减少,提示依达拉奉可以减轻自由基对mtDNA的氧化损伤,保护VD大鼠的神经功能.