补肾填精法对阿尔茨海默病小鼠PI3K/Akt通路激活及氧化应激的影响

Effects of kidney-tonifying,essence-replenishing method on PI3K /Akt activation and oxidative stress in Alzheimer mice

目的探讨补肾填精法对阿尔茨海默病(AD)小鼠脑组织氧化应激及学习记忆能力的影响。方法雄性APPsw/PS1ΔE9转基因小鼠,灌服地黄饮子水煎液150天。避暗实验检测小鼠学习记忆能力;检测小鼠脑组织中Akt、GSK-3β的磷酸化水平,Bax、Bcl-2蛋白表达,谷胱甘肽过氧化物酶(GSH-PX)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量。结果地黄饮子可显著延长AD小鼠进入暗室的潜伏期并减少错误次数,提高SOD、GSH-PX活性,降低MDA含量,促进Akt、GSK-3β激活,降低Bax/Bcl-2比值(P<0.01或P<0.05)。结论地黄饮子可通过激活PI3K/Akt通路,抑制AD小鼠脑内氧化应激和细胞凋亡,保护线粒体,改善学习记忆。

Objective To investigate the effects of kidney-tonifying, essence-replenishing method on oxidative stress and learning and memory ability in Alzheimer disease （AD） mice. Methods Male APPsw/PSIAE9 mice were orally administrated with Dihuang Yinzi for 150 days. The ability of learning and memory of mice was examined by step through test. The phosphorylation level of Akt and GSK-3β, the expression of Bax and Bcl-2, the activity of glutathione peroxidase （GSH-PX） and superoxide dismutase （SOD） , and the content of malondialdehyde （MDA） in mice brain were assayed. Results Dihuang Yinzi prolonged the incubation period for AD mice entering the darkroom, and reduced error times （P 〈0. 01 or P 〈0. 05）. With Dihuang Yinzi treatment, the activity of SOD and GSH-PX and the activation of Akt and GSK-3~ were elevated （P 〈0. 01 or P 〈0. 05） , the content of MDA and ratio of Bax/Bcl- 2 were decreased （P 〈 0. 01 or P 〈 0. 05 ）. Conclusion With activating PI3K/Akt pathway, inhibiting brain oxidative stress and cell apoptosis in AD mice and protecting mitochondria, Dihuang Yinzi could improve the ability of learning and memory.