柴胡疏肝散对阿尔茨海默病大鼠记忆功能的相关研究  

Effect of Chaihu Shugan San on Memory Function in Alzheimer's Disease Rats

作　　者：赵唯贤[1] 李高申[2] 范新六 薛红莉[1] 黄显峰[1] 裴瑞[1] 李宁宁[1] 王黎[1] 

机构地区：[1]河南职工医学院,郑州451191 [2]黄河科技学院,郑州450005 [3]中国中医药国际合作中心,北京100101

出　　处：《中国实验方剂学杂志》2012年第10期207-210,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：河南省教育厅自然科学研究计划项目(2010C360001)

摘　　要：目的:探讨柴胡疏肝散在阿尔茨海默病(Alzheimer's diseas,AD)治疗中的意义。方法:大鼠随机分6组,其中模型组(C),柴胡疏肝散低剂量和高剂量组(D,E),补肾组(F)均采用D-半乳糖(ip)和β-淀粉样蛋白(Aβ)双侧海马注射联合造模,Aβ造模成功后的第9 d,D,E组分别ig给予柴胡疏肝散10,20 g·kg-1,F组给予脑力宝20 g·kg-1。各组均在每天上午9:00按10 mL·kg-1的容积ig给药,连续ig 28 d。ig前后分别进行水迷宫行为学检测,最后处死动物取海马进行相关指标信使RNA(mRNA)表达的相对含量测定。结果:柴胡疏肝散高剂量组ig前后迷宫寻找平台时间分别为(17.34±3.35),(12.78±2.54)s,补肾组分别为(17.79±2.25),(14.11±2.66)s,2组ig前后比较及ig后与同期的模型组比较均有显著差异(P<0.01)。给药后,2组海马蛋白质磷酸酶-2A(PP-2A)mRNA的表达值分别为(0.230 4±0.035),(0.199 4±0.022 2),与模型组(0.099±0.028 8)比较明显增加(P<0.01),而细胞周期依赖性蛋白激酶5(CDK-5)和糖原合成酶激酶3β(GSK-3β)mRNA的表达高剂量组,补肾组比较及高剂量,低剂量组比较均明显降低(P<0.01)。结论:柴胡疏肝散通过抑制动物海马GSK-3β,CDK-5表达而增强PP-2A的表达,可以逆转Aβ诱导的tau蛋白过度磷酸化,从而对记忆、认知障碍起到积极的调节作用。Objective： To investigate the effect of Chaihu Shugan San on memory function in Alzheimer＇s disease （AD） rats. Method： Rats were randomly divided into six groups, including the model group （C）, Chaihu Shugan San low-dose and high dose group （D, E） , kidney group （F） are used by D-galactose andβ- protein （Aβ） hippocampus co-injection modeling, Aβ after the success of modeling the first 9 d, D, E groups were given ig C haihu Shugan San 10, 20 g. kg-1, F group was given Naolibao 20 g. kg-1. Each group were 9：00 in the morning by 10 mL. kg-1 ig administration of volume, continuous ig 28 d. ig before and after the water maze behavioral testing, the last animals were killed for hippocampus-related indicators messenger RNA （mRNA） expression relative determination. Result： Chaihu Shugan San maze before and after high-dose group ig time finding the platform, respectively （17.34 ±3.35）, （12.78 ±2.54） s, kidney groups were （17.79 ±2.25）, （ 14. 11 ± 2.66） s, before and after the two groups of ig and ig with the same period in the model group, there was a significant difference （P 〈 0.01 ）. After administration of the two groups hippocampal protein phosphatase-2A （PP-2A） mRNA expression values were （0. 230 4 ± 0.035）, （0. 199 4 ± 0.022 2）, with the model group （0. 099 ± 0. 028 8） more significantly increased （P 〈 0.01 ） , and cell cycle-dependent protein kinase 5 （ CDK-5 ） and glycogen synthase kinase 3/3 （GSK-3/3） mRNA expression in high-dose group, kidney and high-dose group, low dose group were significantly lower （P 〈 0.01 ）. Conclusion： Chaihu Shugan San hippocampus by inhibiting GSK-3/3, CDK-5 expression enhanced the expression of PP-2A, can reverse the Aβ-induced tau protein hyperphosphorylation, and thus the memory, cognitive disorders play a positive regulatory the role.

关 键 词：阿尔茨海默病 学习记忆 糖原合成酶激酶3Β 细胞依赖性蛋白激酶5 蛋白磷酸酶2A 柴胡疏肝散 

分 类 号：R285.5[医药卫生—中药学]