柴胡疏肝散对阿尔茨海默病大鼠记忆功能的相关研究

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9d,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.

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

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 and β-protein(Aβ) hippocampus co-injection modeling,Aβ after the success of modeling the first 9 d,D,E groups were given ig Chaihu 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 3β(GSK-3β) 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-3β,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.