金纳多注射液对局灶性脑缺血再灌注后神经细胞凋亡及相关蛋白的动态影响

Effects of Ginaton on the dynamic changes of apoptosis and correlative proteins in rats after focal cerebral ischemia and reperfusion

目的研究金纳多注射液对大鼠局灶性脑缺血再灌注后神经细胞凋亡及Bcl2、Bax蛋白表达的影响。方法建立大鼠大脑中动脉缺血再灌注模型。60只Wistar雄性大鼠被随机分为假手术组、缺血组和金纳多治疗组。缺血组和金纳多治疗组分别在脑缺血再灌注后6,12,24,48h处死,应用免疫组化染色及原位细胞凋亡检测脑组织Bcl2、Bax蛋白表达及凋亡细胞数。结果缺血组和金纳多治疗组凋亡细胞数于脑缺血再灌注后24h达高峰,金纳多治疗组各时点凋亡细胞数均明显少于缺血组(P<0.01)。缺血组和金纳多治疗组Bcl2表达于脑缺血再灌注后12h达高峰,金纳多治疗组各时点Bcl2蛋白表达均明显高于缺血组(P<0.01)。缺血组和金纳多治疗组Bax蛋白表达于脑缺血再灌注后24h达高峰,金纳多治疗组各时点Bax蛋白表达均明显低于缺血组(P<0.01)。结论金纳多注射液可能通过上调Bcl2蛋白表达,下调Bax蛋白表达,对脑缺血再灌注损伤起保护作用。

Objective: To study the effects of Ginaton on apoptosis and the expression of Bcl-2 and Bax after focal cerebral ischemia and reperfusion. Methods: The model of middle cerebral artery occlusion (MCAO) and reperfusion was set up. Sixty Wistar male rats were randomly divided into sham-operated group, ischemic group, and Ginaton-treated group. The rats in ischemic group and Ginaton-treated group were killed 6,12, 24, 48 hours after cerebral ischemia and reperfusion. The brain sections were used for terminal deoxynucleotidyl transferase dUTP mickend labeling (TUNEL) staining and Bcl-2, Bax immunohistochemical staining. Results: The apoptotic cells of ischemic group and Ginaton-treated group reached peak 24 hours after cerebral ischemia and reperfusion. The apoptotic cells of Ginaton-treated group on different time points significantly decreased compared with that of ischemic group (P<0.01). The expression of Bcl-2 positive cells in ischemic group and Ginaton-treated group reached peak 12 hours after cerebral ischemia and reperfusion. The expression of Bcl-2 positive cells in Ginaton-treated group on different time points significantly increased compared with that in ischemic group (P<0.01). The expression of Bax positive cells in ischemic group and Ginaton-treated group reached peak 24 hours after cerebral ischemia and reperfusion. The expression of Bax positive cells in Ginaton-treated group on different time points significantly decreased compared with that in ischemic group (P<0.01). Conclusion: Ginaton can decrease the number of apoptotic cells after cerebral ischemia and reperfusion by up-regulating Bcl-2 and down-regulating Bax.