氟桂利嗪对缺血再灌注后沙土鼠CA1区迟发性神经元死亡的保护作用

目的　探讨迟发性神经元死亡(DND)发生的机制及氟桂利嗪对海马CA1区神经元的保护作用。方法　将实验动物随机分为脑缺血再灌注组、给药组及假手术组。采用免疫组织化学染色及电镜下观察脑组织病理变化的方法观察缺血再灌注后海马各亚区谷氨酸及神经生长因子的表达变化及氟桂利嗪的神经保护作用。结果　脑缺血再灌注第1天和第2天海马各亚区谷氨酸表达增高,与药物组及对照组比较差异显著(P <0 .0 1) ,其第2天表达增高最为显著,与第1天比较P <0 .0 1;脑缺血再灌注第1天和第2天海马CA1区神经生长因子表达增高,与药物组及对照组比较P <0 .0 1,其第2天表达增高最为显著,与第1天比较P <0 .0 5 ;脑缺血再灌注第7天见海马CA1区神经元广泛性脱失,胶质细胞大量增生,缺血再灌注组和给药组海马CA1区存活的神经元均少于对照组(P <0 .0 1) ,但给药组存活的神经元数目又明显多于缺血再灌注组(P <0 .0 1)。结论　氟桂利嗪可以阻止谷氨酸的持续性高表达及神经生长因子的表达下降,从而对DND的发生起到保护作用。

Protective effect of flunarizine on delayed neuronal death in CA1 area after ischemia-reperfusion

objective To explore the mechanism leading to delayed neuronal death(DND) and the protective effect of flunarizine on neurons in CA1 area of hippocampus.Method The change of expression of glutamate and nerve growth factor(NGF) in every subregion of hippocampus after ischemia-reperfusion and neuroprotectine effect of flunarizine were observed with immunohistochemical method.Results (1)Expression of glutamate in every subregion of hippocampus increased on the first and second days after cerebral ischemia-reperfusion and had significant difference compared with both medication group and control group(P<0.01).The expression on the second day was more significant and had apparent difference compared with that on the first day(P<0.01).(2)Expression of NGF in CA1 area of hippocampus increased on the first and second days after cerebral ischemia-reperfusion and had significant difference compared with both medication group and control group(P<0.01).Expression of NGF on the second day was more significant with obvious difference compared with that on the first day (P<0.05).(3)On the seventh day after cerebral ischemia-reperfusion there were extensive disappearance of neurons and massive proliferation of neuroglial cells in CA1 area of hippocampus,and the number of alive neurons in CA1 area of hippocampus either in ischemia-reperfusion group or medication group was lower than that in control group(P<0.01).However, the number of alive neurons in medication group was significantly greater than that in ischemia-reperfusion group(P<0.01).Conclusion Flunarizine can prevent glutamate from continuous high level of expression and the expression of NGF from decreasing, thus exerting protective effect on DND.