小檗碱对小鼠全脑缺血后神经元凋亡相关基因的影响

Effects of berberine on neuronal apoptosis related gene after global cerebral ischemia in mice

目的 探讨小檗碱对小鼠全脑缺血后神经元凋亡相关基因的影响 ,以了解小檗碱保护脑缺血的机制 ,为其开发利用提供理论依据。方法 利用改良的Pulsinelli Brierley 4血管闭塞法制成小鼠全脑缺血再灌注动物模型。小檗碱用量为 1mg/kg ,于术前 30min ,术后每日 1次 ,腹腔注射。免疫组织化学技术检测凋亡相关基因Bcl 2 ,Bax蛋白的表达。结果 正常组海马区未见Bcl 2或Bax蛋白表达 ;缺血组再灌注 6h海马CA3 区可见Bcl 2阳性细胞 ,2 4h达到高峰 ,48h开始下降 ;小檗碱治疗组再灌注 2 4h、48h及 16 8hB cl 2阳性细胞数明显减少 (P <0 .0 1)。缺血组再灌注 6h海马CA1区可见Bax阳性细胞 ;48h达高峰 ;16 8h明显下降 ;小檗碱组再灌注 2 4h ,48h及 16 8hBax阳性细胞数明显减少 (P <0 .0 1)。结论 小檗碱可以增加小鼠全脑缺血后海马CA3 区bc1 2基因的表达 ,降低CA1区Bax基因的表达 ,从而减少凋亡的发生 ,可能为其保护脑缺血的机制之一。

Objective To investigate the effects of Berberine on neuronal apoptosis related gene after global cerebral ischemia in mice.Methods The model of transient global cerebral ischemia was made using the Pulsinelli Brierley 4 vessels occlusion methods.Berberine (1mg/kg) was administered intraperitoneally 30 minutes before ischemia and once a day after ischemia.Bcl 2 and Bax immunohistochemstry staining in hippocampas after global ischemia were used to detect Bax and Bcl 2 protein.Results The Bcl 2 positive cells in the hippocampal CA 3 fields were detected at 6 hours during reperfusion.They got to peak at 24 hours and decrease at 48 hours.The Bcl 2 positive cells of Berberine group increased significantly at 24 hours, 48 hours and 168 hours compared with ischemia group ( P < 0.01 ).The Bax positive cells appeared in the hippocampal CA 1 fields at 6 hours after global ischemia, increased at 24 hours and got to peak at 48 hours.The Bax positive cells of Berberine group reduced significantly at 24 hours, 48 hours and 168 hours compared with ischemia group ( P < 0.01 ).Conclusion Berberine may increase the Bcl 2 protein expression in the hippocampal CA 3 field and decrease the Bax protein expression during reperfusion after global cerebral ischemia in mice, which might be one of the mechanisms that Berberine protect cerebral ischemia.