六味地黄汤对快速衰老小鼠认知功能及碱性成纤维细胞生长因子/Notch通路表达的影响

Study on Effects of Liuwei Dihuang Decoction on Cognitive Function and Expression of b FGF/Notch Pathway in Rapid Aging Mice

目的观察六味地黄汤对快速衰老小鼠认知功能及碱性成纤维细胞生长因子(b FGF)/Notch信号通路表达的影响,探讨其改善认识障碍的作用机制。方法将小鼠随机分为正常组、模型组、阳性对照组和六味地黄汤高、中、低剂量组,颈部皮下注射D-半乳糖制作快速衰老小鼠模型,各给药组给予相应药物灌胃。Morris水迷宫系统检测大鼠学习记忆能力,免疫组化检测小鼠脑组织b FGF、Notch1、Hes1的表达。结果与正常组比较,模型组小鼠潜伏期延长、跨台次数减少(P<0.01);与模型组比较,各给药组小鼠潜伏期缩短、跨台次数增多(P<0.01),六味地黄汤高剂量组较六味地黄汤中、低剂量组和阳性对照组效果明显(P<0.01);各给药组小鼠b FGF、Notch1、Hes1阳性细胞数表达较模型组升高(P<0.05,P<0.01),六味地黄汤高剂量组较六味地黄汤中、低剂量组和阳性对照组升高明显(P<0.01)。结论六味地黄汤可能通过增加b FGF的表达,激活Notch信号通路,达到改善衰老小鼠认知功能障碍。

Objective To observe the effects of Liuwei Dihuang Decoction on cognitive function and expressionof bFGF/Notch pathway in rapid aging mice; To discuss the mechanism of action of improving cognitive disorders.Methods Mice were randomly divided into normal group, model group, positive control group, and high-, medium-,and low-dose Liuwei Dihuang Decoction groups. D-galactose subcutaneously injected method was used to establishthe rapid aging mice model. Each medication group was given relevant medicine for gavage. Morris water mazesystem was used to determine the changes of the learning and memory of mice. Immunohistochemical method wasused to detect the expressions of bFGF, Notch1 and Hes1 of mice brain tissue. Results Compared with the normalgroup, incubation lengthened and the times of building collapsed decreased in the model group (P<0.01); Comparedwith the model group, incubation shortened and the times of building collapsed increased in all medication groups(P<0.01), and high-dose Liuwei Dihuang Decoction group was more obvious than medium- and low-dose LiuweiDihuang Decoction groups and positive control group (P<0.01); the expressions of bFGF, Notch1 and Hes1 in allmedication groups increased (P<0.05, P<0.01), and high-dose Liuwei Dihuang Decoction groups were moreobvious than medium- and low-dose Liuwei Dihuang Decoction groups and positive control group (P<0.01).Conclusion Liuwei Dihuang Decoction can improve D-galactose induced cognitive disorders of rapid aging mice,increase the expression of bFGF, activate Notch signaling pathways.