神经节苷脂GM1联合尼莫地平对脑缺血再灌注后细胞凋亡及凋亡相关蛋白表达的影响

目的:探讨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6h,12h,24h,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,差异有显著性(P<0.05)。2与模型组比较,药物治疗组随再灌注时间延长,Bcl-2蛋白表达明显上调;而Bax蛋白表达随再灌注时间的延长,表达逐渐减弱,有显著性差异(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。

Protective effect of GM1 ganglioside combined nimodipine on nerve cells after cerebral ischemia-reperfusion

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） and treatment group （n = 16）.A middle cerebral artery ischemia-reperfusion （MCAO） model was reproduced with the intraluminal suture method,reperfusion 6h,12h,24h,72h after ischemia 2h.TUNEL assay apoptosis of nerve cells.Bcl-2,Bax protein was measured by immunohistochemistry staining,and analyzed statistically.Results：① Compared with the model group,apoptotic nerve cell counts reduced significantly with the extension of reperfusion in combination therapy,the difference was significant （P 0.01）.②Compared with the model group,expression of Bcl-2 gradually increased with the extension of reperfusion in combination therapy.While expression of Bax expression gradually decreased with the extension of reperfusion.There was a significantly difference between them （P 0.05）.Conclusion：Gangliosides combined nimodipine intervention treatment can reduce neuronal apoptosis in the ischemic penumbra,through up-regulating Bcl-2 expression and reduce Bax expression,and thus play a role in nerve cell protection.