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目的:探讨补阳还五汤对脑缺血再灌注大鼠不同时期海马CA4区Hes1和Hes5表达的影响,阐明Notch信号传导系统在补阳还五汤对局灶性脑缺血再灌注大鼠神经修复作用中的调节作用。方法:清洁级SD大鼠63只随机分为补阳还五汤组(Group BYHWT)、脑缺血再灌注损伤模型组(Group CIRI)、假手术组(Group Sham)。采用大脑中动脉阻塞线拴法(MCAO法)建立BYHWT组和CIRI组的局灶性脑缺血再灌注大鼠模型。脑缺血2 h,分别再灌注10 d、19 d和28 d,采用免疫组化SP法检测海马CA4区Hes1和Hes5表达的阳性细胞数目,并进行单因素方差分析(one way ANOVA),两组间均数差异性比较采用t检验。结果:术后10 d和19 d,CIRI组大鼠海马CA4区的Hes1和Hes5阳性细胞密度较Sham组大(P<0.01)。BYHWT组大鼠海马CA4区Hes1和Hes5阳性细胞密度较CIRI组及Sham组都大(P<0.01);而在术后28 d,则显著低于CIRI组与Sham组(P<0.01)。CIRI组和BYHWT组术后19 d大鼠海马CA4区阳性细胞密度分别较术后10天增加(P<0.01);而术后28天阳性细胞密度较术后19天降低(P<0.01)。结论:补阳还五汤在脑缺血再灌注损伤早中期通过上调大鼠海马CA4区Hes1和Hes5的表达,而在晚期通过下调其表达,而对局灶性脑缺血再灌注损伤产生神经修复作用,该作用的发挥可能是通过控制Hes1和Hes5的表达水平来调控Notch信号传导系统,进而调节NSCs的增殖与分化。
Objective: To investigate the effect of Buyang Huanwu decoction on the expression of Hes1 and Hes5 in hippocampal CA4 in different periods of cerebral ischemia reperfusion in rats, and to elucidate the mechanism of Buyang Huanwu decoction on focal cerebral ischemia-reperfusion rats The role of nerve repair in the regulation. Methods: Sixty clean SD rats were randomly divided into Group BYHWT group, Group CIRI group and Group Sham group. The model of focal cerebral ischemia-reperfusion in BYHWT group and CIRI group was established by occlusion of middle cerebral artery occlusion (MCAO). Two hours after cerebral ischemia, reperfusion 10 d, 19 d and 28 d respectively. Immunohistochemical SP method was used to detect the number of Hes1 and Hes5 positive cells in hippocampal CA4 region, and one way ANOVA Differences between groups were compared using t test. Results: On day 10 and day 19, the positive cells of Hes1 and Hes5 in hippocampal CA4 area of CIRI group were significantly higher than those of Sham group (P <0.01). The density of Hes1 and Hes5 positive cells in hippocampal CA4 area of BYHWT group was significantly higher than that of CIRI and Sham groups (P <0.01), but significantly lower than that of CIRI and Sham groups at 28 d after operation (P <0.01). The positive cell density of hippocampal CA4 region in CIRI group and BYHWT group was significantly higher than that of the control group (P <0.01) on the 19th day after operation, while the positive cell density was decreased on the 28th day after operation (P <0.01). Conclusion: Buyang Huanwu Decoction can increase the expression of Hes1 and Hes5 in the hippocampal CA4 region in the early and mid cerebral ischemia-reperfusion injury, but in the later stage, through down-regulating the expression of Hes1 and Hes5, Repair, this effect may play a role in regulating the Notch signaling system by controlling the expression levels of Hes1 and Hes5, thereby regulating the proliferation and differentiation of NSCs.