六味地黄汤对快速衰老小鼠认知功能及Wnt3a、GSK-3β表达的影响

Effects of Liuwei Dihuang Decoction on Recognition and the Expression of Wnt3a and GSK-3β in Senescence Accelerated Mice

目的研究六味地黄汤对D-半乳糖(D-gal)致快速衰老小鼠认知功能及Wnt3a、GSK-3β表达的影响。方法以500 mg/(kg·d)的D-半乳糖颈部皮下注射复制快速衰老小鼠模型,将动物随机分为正常组,模型组,六味地黄(简称六味)高、中、低剂量组,Vit E组,给予相应干预,历时8周。观察小鼠的体质量变化,采用Morris水迷宫实验评价小鼠的认知功能,免疫组化法、RT-q PCR法检测Wnt3a、GSK-3β的表达。结果六味地黄汤对快速衰老小鼠体质量及水迷宫实验的影响:模型组与正常组比较,差异具有显著统计学意义(P<0.01);各用药组与模型组比较,差异具有显著统计学意义(P<0.01);六味高剂量组与其他用药组比较,差异具有统计学意义(P<0.05);六味地黄汤对快速衰老小鼠认知功能及Wnt3a、GSK-3β表达的影响:模型组与正常组比较,差异具有显著统计学意义(P<0.01),各用药组与模型组比较,差异具有显著统计学意义(P<0.01),六味高剂量组与其他用药组比较,差异具有显著统计学意义(P<0.01)。结论六味地黄汤可以有效改善D-半乳糖致快速衰老小鼠的学习记忆障碍;增加衰老小鼠Wnt3a的表达,激活Wnt信号通路,下调GSK-3β的表达可能是六味地黄汤延缓衰老健脑益智的作用机制。

Objective To study the effect of Liuwei Dihuang Decoction（LWDHD） on recognition, Wnt3 a and GSK-3β in D-galactose induced senescence accelerated mice. Methods The senescence accelerated mice were injected 500 mg/（kg·d） of D-galactose subcutaneously copy rapid, the animals were randomly divided into normal group, model group, high dose, medium dose and low dose of LWDHD groups and Vit E group, which were given different processing. After gavage 10 m L/（Kg·d） for eight weeks, the mice body quality change was changed, cognitive function in mice was evaluated by line Morris water maze experiment, the expression of Wnt3 a and GSK-3β were detected by immunohistochemical and RT-q PCR methods. Results Compared with normal group and other groups, the weight gain of body mass in model group was lesser（P〈0.05）, the incubation period was longer and cross platform times was more（P〈0.05）; Compared with normal group, the diffrences of the body quality increases, the incubation period and cross platform number in high dose of LWDHD group were not statistically significant（P〉0.05）; Compared with Vit E group, the body quality and the ability of learning and memory in low dose of LWDHD group have no statistical significance（P〈0.05）; The high dose of LWDHD group and other groups were statistically significant（P〈0.05）. The result showed high consistency by immunohistochemical method and RT-q PCR detection. Compared with the model group, the low expression of Wnt3 a, high activity of GSK-3β in high dose of LWDHD group, the difference was statistically significant（P〈0.01）; Compared with the medium and low dose of LWDHD groups and Vit E group, the high expression of Wnt3 a and low activity of GSK-3β in the high dose of LWDHD group were statistically significant（P〈0.01）.Conclusion Liuwei Dihuang Decoction can improve the learning and memory dioders in D-galactose induced senescence accelerated mice. The mechanism of Liuwei Dihuang Decoction in anti-aging and promoting intelligence could be increasing the Wnt3 a expression in aging mice, activation of Wnt signaling pathways, and down-regulating GSK-3β expression.