大麻素受体1高选择性激动剂ACEA对脑缺血-再灌注后线粒体生物发生的影响  

The effect of CB1R highly selective agonist ACEA on mitochondrial biogenesis after cerebral ischemia reperfusion

作　　者：江涛[1] 魏海东[1] 郭钒[1] 高琴琴[1] 翟茜[1] 王强[1] 

机构地区：[1]第四军医大学西京医院麻醉科,西安市710032

出　　处：《临床麻醉学杂志》2015年第5期476-480,共5页Journal of Clinical Anesthesiology

基　　金：国家自然科学基金(81072888)

摘　　要：目的观察大麻素受体1(CB1R)高选择性激动剂ACEA对脑缺血-再灌注后线粒体生物发生的影响。方法 24只成年雄性SD大鼠随机均分为三组:假手术组(S组),生理盐水组(C组)和ACEA 1mg/kg组(A组)。C组和A组制备大脑中动脉阻塞(middle cerebral artery occlusion,MCAO)模型,在脑缺血-再灌注后1h腹腔注射生理盐水(C组)或ACEA 1mg/kg(A组)。脑缺血-再灌注后4h采用Western blot检测细胞核呼吸因子-1(Nrf-1)与线粒体转录因子A(Tfam)蛋白含量,并于脑缺血-再灌注后4h应用电镜方法观察线粒体体积与数量变化。结果与C组比较,在脑缺血-再灌注后4hA组Nrf-1和Tfam蛋白含量明显升高(P<0.05);脑缺血-再灌注4h后A组线粒体体积占细胞质的百分比明显增加(P<0.05)。结论在脑缺血-再灌注后CB1R高选择性激动剂ACEA通过诱导线粒体生物发生发挥神经保护作用。Objective To investigate the role of mitochondrial biogenesiss in the therapeutic effect of cannabinoid receptor 1（CB1R）highly selective agonist ACEA after cerebral ischemia reperfusion.Methods Adult male Sprague-Dawley（SD）rats were randomly divided into 3groups（n=8）：Sham group（group S）,Control group（group C）,ACEA 1mg/kg group（group A）.Cerebral ischemic injury was induced by middle cerebral artery occlusion（MCAO）.ACEA 1mg/kg（group A）and vehicle（group C）were injected intraperitoneally 1hafter cerebral ischemia and reperfusion.The expression of Nrf-1and Tfam were analyzed by Western blot at 4hafter reperfusion.The mitochondrial volume and numbers was detected by electron microscopic（EM）at 4hafter reperfusion.Results At4 hafter reperfusion,the expression of Nrf-1and Tfam was obviously improved in group A compared with group C（P〈0.05）.The volume of mitochondria was significantly improved in group A compared with group C（P〈0.05）.Conclusion CB1 Rhighly selective agonist ACEA can induce mitochondrial biogenesis at the beginning of cerebral ischemia reperfusion.This may be involved in the neuroprotective effect induced by ACEA.

关 键 词：内源性大麻素系统 脑缺血-再灌注 线粒体生物发生 脑保护 

分 类 号：R285.5[医药卫生—中药学]