【摘要】 目的:观察沙土鼠前脑缺血时海马区P53蛋白的表达并探讨氯化锂对其干预作用。方法:夹闭沙土鼠双侧颈总动脉5min,制备前脑缺血损伤模型。沙土鼠54只,随机分为假手术组(SH组)、缺血再灌注组(IR组)、氯化锂预处理组(LI组)。依术后处死动物时间的不同,每组再分为3个亚组(SH1d、SH3d、SH7d;IR1d、IR3d、IR7d和LI1d、LI3d、LI7d),每个亚组6只动物。苏木精-伊红染色观察海马区病理变化,免疫组化(SP法)检测海马CA1区P53蛋白的表达。结果:①苏木精-伊红染色LI组中LI3d、LI7d亚组海马区神经元损伤程度明显较IR组中相对应的IR3d、IR7d亚组为轻,LI3d、LI7d亚组海马CA1区存活锥体细胞数明显多于相对应的IR3d、IR7d亚组(P<0.01);②P53免疫组化IR组于再灌注后1天P53蛋白表达增高,3天后显著增高,再灌注后7天有所下降,但仍高于SH组;LI组P53蛋白的表达显著低于相应的IR组(P<0.01)。结论:①氯化锂预处理能显著减少沙土鼠短暂前脑缺血后海马CA1区神经元死亡;②下调促凋亡基因P53蛋白的表达可能是氯化锂产生脑保护作用的机制之一。更多还原

【Abstract】 Objective: To investigate the expression of P53 protein in hippoc am pus of gerbils following forebrain ischemia and the mechanism of neuroprotective effect of lithium chloride. Methods: The forebrain ischemia model of gerbil was prepared by clamping the bilateral common carotid arteries for 5 min. Fifty fou r gerbils were randomly divided into sham operation group(SH group, n=18), ische mia reperfusion group (IR group, n=18),preconditioning with lithium chloride gro up(LI group, n=18). SH, IR and LI groups were further divided into three subgrou ps respectively(SH1d,SH3d,SH7d;IR1d,IR3d,IR7d;LI1d,LI3d,LI7d), with 6 gerbils in each subgroup(n=6). The pathological change in hippocampus of gerbils was exami ned by HE staining. The expression of P53 protein in hippocampal CA1 region was examined by immunohistochemistric staining (SP method). Results: ①HE staining T he numbers of living pyramidal neuron in CA1 region of LI3d or LI7d were signifi cantly higher than those of IR3d or IR7d(P< 0.01). ②Immunohistochimstry In IR g roup, the expression of P53 protein was increased at 1 day after reperfusion, ob viously increased at 3 day and significantly decreased at 7 day after reperfusio n, but still maintained at a high level. The expression of P53 protein in LI gro up was obviously lower than that in IR group(P< 0.01). Conclusion: Lithium chlor ide can significantly reduce the death of neuron in hippocampus of gerbils after forebrain ischemia. The down-regulation of expression of P53 protein is one of the mechanisms of the neuroprotective effect by lithium chloride. [更多还原