神经节苷脂联合尼莫地平对脑缺血半暗带凋亡蛋白Bcl-2、Bax及Bcl-2/Bax比值的影响

目的观察大鼠脑缺血再灌注损伤后神经节苷脂GM1联合尼莫地平治疗对神经细胞凋亡及凋亡相关蛋白Bcl-2、Bax表达的影响。方法 36只清洁级健康雄性SD大鼠随机分为假手术组（n=4）模型组（n=16）药物治疗组（n=16）。线栓法制备大脑中动脉缺血再灌注模型（MCAO模型）,于缺血2h再灌注6、12、24、72h。采用TUNEL法检测神经细胞凋亡,免疫组织化学法染色检测Bcl-2、Bax蛋白,并进行统计学分析。结果①与模型组比较,药物治疗组神经细胞凋亡计数随再灌注时间的延长显著减少,差异有统计学意义（P〈0.05）;②药物治疗组随再灌注时间延长,缺血半暗带区Bcl-2表达逐渐增强、以及Bax表达逐渐减弱,使缺血2h再灌注12h,Bcl-2/Bax比值达到高峰。与模型组比较,差异有统计学意义（P〈0.05）。结论在脑缺血半暗带区,神经节苷脂联合尼莫地平干预治疗,通过上调Bcl-2表达,以及下调Bax表达,能够减少神经细胞凋亡,从而发挥神经细胞保护作用。

The effect of ganglioside combined nimodipine on apoptotic protein Bcl-2, Bax of cerebral ischemic penumbra and the ratio of Bcl-2/Bax

Objective To observe the effect of brain protective agents on neuronal apoptosis and apoptosis-related proteins Bcl-2,Bax expression after focal cerebral ischemia reperfusion injury.Methods 36 clean grade healthy male SD rats were randomly divided into sham-operated group（n=4） model group（n=16） combined treatment group（n=16）.A middle cerebral artery ischemia-reperfusion（MCAO） model was reproduced with the intraluminal suture method,reperfusion 6、12、24、72h after ischemia 2h.TUNEL assay apoptosis of nerve cells.Bcl-2,Bax protein was me asured by immunohistochemistry staining,and analyzed statistically.Results Compared with the model group,apoptotic nerve cell counts reduced significantly with the extension of reperfusion in combination therapy,the difference was significant（P0.01） Compared with the model group,expression of Bcl-2/Bax expression gradually decreased with the extension of reperfusion.There was a significantly difference between them（P0.05）.Conclusion gangliosides combined nimodipine intervention treatment can reduce neuronal apoptosis in the ischemic penumbra,through up-regulating Bcl-2 expression and reduced Bax expression,and thus play a role in nerve cell protection.