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中的调节作用  

Effects of Notch Conduction System on neural repair of Buyang Huanwu Decoction to rats with focal cerebral Ischemic-Reperfusion injury

作　　者：涂建锋[1] 魏良浩[1] 周晟昂[1] 张可[1] 陈环[1] 张美齐[1] 蔡文伟[1] 杨悦[2] 

机构地区：[1]浙江省人民医院急诊医学科,浙江杭州310014 [2]浙江医学高等专科学校,浙江杭州310053

出　　处：《中华中医药学刊》2015年第3期675-678,I0012-I0014,共7页Chinese Archives of Traditional Chinese Medicine

基　　金：浙江省中医药科学研究基金计划项目(2010ZA003);浙江省科技厅公益性技术应用研究计划实验动物平台项目(2013C37022)

摘　　要：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 expressions of Hes- 1 and Hes- 5in the CA4 zone of hippocampus of focal ischemic rats with cerebral ischemia- reperfusion injury and illuminate the probable molecular mechanism of the effect of the decoction on the proliferation and differentiation of the neural stem cells.Methods： 63 SD rats in clean level were randomly divided into Buyang Huanwu Decoction group,cerebral ischemia-reperfusion injury（ CIRI） group and sham group. Middle cerebral artery occlusion（ MCAO） was performed to establish the focal cerebral I / R injury model. Each 7 rats in one group were performed with 10 days,19 days and 28 days after occlusion with 2 hours respectively. The positive cell number of Hes- 1 and Hes- 5 in the CA4 zone of hippocampus was observed with immunohistochemical techniques. One way ANOVA and t test were used to analyze the data. Results： The positive cell density of Hes- 1 and Hes- 5 in CA4 zone of hippocampus in CIRI group following 10 days and 19 days reperfusion was significant larger than that of sham group（ P〈 0. 01）. The positive cell density in Buyang Huanwu Decoction group following 10 days and 19 days reperfusion was significant larger than that of both CIRI group and sham group（ P〈 0. 01） and also was significantly lower than that of CIRI group and sham group following 28 days reperfusion（ P〈 0. 01）. The positive cell density in CIRI group and Buyang Huanwu Decoction group following 28 days reperfusion was lower than that of 19 days reperfusion（ P〈 0. 01） which was larger than that of 10 days reperfusion（ P〈 0. 01）. Conclusion： The neural repair effect of Buyang Huanwu Decoction to focal cerebral I / R injury was performed through up- regulation of Hes- 1 and Hes- 5 in CA4 zone of the hippocampus in the early and mid term and down- regulation in the late phase. The Notch signal conduction system was probably regulated by the expressions of Hes- 1 and Hes- 5 to adjust the proliferation and dif

关 键 词：补阳还五汤 缺血再灌注 海马 Hes-1 Hes-5 

分 类 号：R285.5[医药卫生—中药学]