依达拉奉干预对大鼠脑出血模型细胞凋亡相关通路的影响

目的研究脑出血后自由基对于细胞凋亡通路的影响。方法将动物随机分为4组,假手术组、模型组、依达拉奉组1（1mg／kg）、依达拉奉组2（3mg／kg）,通过立体定向技术,采用二次注血／退针方法向成年SD大鼠左尾壳核注入自体血80ul,制造大鼠脑出血动物模型。通过免疫组化半定量检测脑出血后肿瘤坏死因子-α（Tumournecrosis factor-alpha,TNF-a）的表达,并通过Westernblot检测脑组织中Caspase-3、8的表达水平。结果出血后模型组和药物干预组TN卜a表达水平有差异。半定量检测Caspase-3、Caspase-8蛋白水平,脑出血后二者均有激活,总体水平模型组和两种剂量药物干预组较假手术高,且模型组表达量高于药物干预组。结论脑出血后自由基可能对于TNF-α表达及分泌具有诱导作用,Caspase-3、Caspase-8蛋白表达水平升高,认为死亡受体通路可能参与脑出血后细胞凋亡,并与自由基水平有关。

Preliminary investigation on free radical-induced apoptosis related pathways in rat model of intracerebral hemorrhage

To investigate the effects of free radical on pathway of cell apoptosis in intracere- bral hemorrhage. Methods Animals were randomly divided into four groups, sham operation group, model group, edaravone group 1 （1 mg/kg）, edaravone group 2 （3 mg/kg）. By Horseley Clarke technique,autob lood（80 ttl）were administered into the left caudate putamen of SD rats in a double administration withdrawal way. Semiquantitative detection of TNF-α expression in intracerebral hemorrhage and detection of Caspase-3, 8 expression and activation in brain tissue were performed by immunohistochemical and Western blot respectively. Results TNF-e expression levels were different between hemorrhage model group and drug intervention groups, which indicated that free radicals and TNF-α levels were relevant, free radicals could induce TNF-αexpression. The results of semiquantitative detection of Caspase-3, Caspase-8 protein levels showed that both were activated in intracerebral hemorrhage, the overall levels in the model group and the two drug intervention groups were higher than the sham, and expression levels in the model group were higher than drug intervention groups. Conelusior, s Free radicals may induce TNF-e expression and secretion in intracerebral hemorrhage, Caspase-3, Caspase-8 protein levels are also elevated, which suggest that the death receptor pathways may be involved in apoptosis in intracerebral hemorrhage, and related with the levels of free radicals.