基于PI3K/Akt/GSK-3β信号通路探讨益智治呆方对AD模型大鼠学习记忆能力的影响及其作用机制  

Explore the Effect of Yizhi Zhidai Recipe(益智治呆方)on the Learning and Memory Ability of AD Model Rats and Its Mechanism Based on PI3K/Akt/GSK-3βSignaling Pathway

作　　者：赵翠霞[1] 江钰[1] 省格丽[1] ZHAO Cui-xia;JIANG Yu;SHENG Ge-li(The Hospital of Traditional Chinese Medicine Affiliated to Xinjiang Medical University,Urumqi Xinjiang 830000,China)

机构地区：[1]新疆医科大学附属中医医院,新疆乌鲁木齐830000

出　　处：《中医药导报》2020年第13期18-22,26,共6页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：新疆维吾尔自治区自然科学基金资助项目(2015211C152)。

摘　　要：目的:观察益智治呆方对阿尔茨海默病(AD)大鼠学习记忆能力的影响,探讨其促进认知功能恢复的作用机制。方法:将50只大鼠随机分为假手术组10只和手术组40只,手术组建立AD大鼠模型后随机分为模型组、治疗组、对照组。术后第10天开始定时灌胃给药,治疗第28天行Y形迷宫检测学习记忆能力,采用免疫组织化学方法观察海马中央注射区β-淀粉样蛋白(Aβ)的表达情况;应用TUNEL试剂盒检测海马中央注射区神经细胞的凋亡情况;采用Western blotting检测PI3K、t-Akt、p-Akt、t-GSK-3β、p-GSK-3β、Bcl-2、Bax的蛋白表达水平。结果:益智治呆方、多奈哌齐均能改善AD大鼠学习记忆能力(P<0.05);与模型组比较,治疗组和对照组海马中央注射区β-淀粉样蛋白表达、凋亡细胞率明显减少(P<0.05),PI3K、p-Akt、p-GSK-3β、Bcl-2等抗凋亡蛋白表达增多(P<0.05),t-GSK-3β、Bax等促凋亡蛋白表达减少(P<0.05);治疗组上述指标与对照组比较,差异均无统计学意义(P>0.05)。结论:益智治呆方能够有效改善AD模型大鼠学习记忆能力,降低Aβ神经毒性,减少神经元细胞凋亡,其机制可能是通过PI3K/Akt/GSK-3β信号通路调控凋亡蛋白表达。Objective: To observe the effect of Yizhi Zhidai recipe on the learning and memory ability of Alzheimer’s disease(AD) rats, and to explore its mechanism of promoting cognitive function recovery. Methods: A total of 50 rats were randomly divided into sham operation group(10 rats)and operation group(40 rats). After the AD rat model was established in the operation group, they were randomly divided into model group,treatment group and control group. On the 10 thpostoperative day, regular intragastric administration was started.On the 28 thday of treatment, a Y-maze was used to test the learning and memory ability, and the expression ofβ-amyloid in the central hippocampal injection area was observed by immunohistochemistry. TUNEL kit was used to detect the apoptosis of nerve cells in the central injection area of the hippocampus. The protein expression levels of PI3K, t-Akt, p-Akt, t-GSK-3β, p-GSK-3β, Bcl-2 and Bax were detected by Western blotting. Results: Both Yizhizhidai recipe and donepezil can improve the learning and memory ability of AD rats(P <0.05). Compared with the model group, the expression of β-amyloid and the rate of apoptotic cells in the central hippocampus injection area of the treatment group and the control group were significantly decrease(P<0.05), the expression of anti-apoptotic proteins such as PI3K, p-Akt, p-GSK-3β, Bcl-2 were increased(P<0.05),and the expression of pro-apoptotic proteins such as t-GSK-3β, Bax were decreased(P <0.05). There was no significant difference in the above indicators between the treatment group and the control group(P >0.05).Conclusion: Yizhi Zhidai recipe can effectively improve the learning and memory ability of AD model rats,reduce Aβ neurotoxicity, and reduce neuronal cell apoptosis. The mechanism may be the regulation of apoptotic protein-related protein expression through PI3K/Akt/GSK-3β signaling pathway.

关 键 词：益智治呆方 阿尔茨海默病 学习记忆能力 Β-淀粉样蛋白 凋亡 PI3K/Akt/GSK-3β信号通路 Bcl-2 Bax 大鼠 

分 类 号：R285.5[医药卫生—中药学]