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二氢杨梅素通过激活 AMPK/SIRT1 信号通路对阿尔茨海默病大鼠模型的保护作用。

Protective role of Dihydromyricetin in Alzheimer's disease rat model associated with activating AMPK/SIRT1 signaling pathway.

机构信息

Qingdao Mental Health Center, 229 Nanjing Road, Qingdao 266034, Shandong, P.R. China.

Qingdao Mental Health Center, 229 Nanjing Road, Qingdao 266034, Shandong, P.R. China

出版信息

Biosci Rep. 2019 Jan 3;39(1). doi: 10.1042/BSR20180902. Print 2019 Jan 31.

Abstract

The aim of the present study was to understand the possible role of the Dihydromyricetin (DHM) in Alzheimer's disease (AD) rat model through regulation of the AMPK/SIRT1 signaling pathway. Rats were divided into Sham group, AD group, AD + DHM (100 mg/kg) group and AD + DHM (200 mg/kg) group. The spatial learning and memory abilities of rats were assessed by Morris Water Maze. Then, the inflammatory cytokines expressions were determined by radioimmunoassay while expressions of AMPK/SIRT1 pathway-related proteins by Western blot; and the apoptosis of hippocampal cells was detected by TdT-mediated dUTP nick end labeling assay. AD rats had an extended escape latency with decreases in the number of platform crossings, the target quadrant residence time, as well as swimming speed, and the inflammatory cytokines in serum and hippocampus were significantly elevated but AMPK/SIRT1 pathway-related proteins were reduced. Meanwhile, the apoptosis of hippocampal cells was significantly up-regulated with decreased Bcl-2 and increased Bax, as compared with Sham rats (all <0.05). After AD rats treated with 100 or 200 mg/kg of DHM, the above effects were significantly reversed, resulting in a completely opposite tendency, and especially with 200 mg/kg DHM treatment, the improvement of AD rats was more obvious. DHM exerts protective role in AD via up-regulation of AMPK/SIRT1 pathway to inhibit inflammatory responses and hippocampal cell apoptosis and ameliorate cognitive function.

摘要

本研究旨在通过调节 AMPK/SIRT1 信号通路,探讨二氢杨梅素(DHM)在阿尔茨海默病(AD)大鼠模型中的可能作用。将大鼠分为假手术组、AD 组、AD+DHM(100mg/kg)组和 AD+DHM(200mg/kg)组。采用 Morris 水迷宫评估大鼠的空间学习记忆能力。然后,采用放射免疫法测定炎性细胞因子的表达,采用 Western blot 测定 AMPK/SIRT1 通路相关蛋白的表达;采用 TdT 介导的 dUTP 缺口末端标记法检测海马细胞凋亡。AD 大鼠的逃避潜伏期延长,平台穿越次数、目标象限停留时间和游泳速度减少,血清和海马中的炎性细胞因子明显升高,而 AMPK/SIRT1 通路相关蛋白减少。与假手术组相比,AD 大鼠的海马细胞凋亡明显上调,Bcl-2 减少,Bax 增加(均<0.05)。AD 大鼠用 100 或 200mg/kg 的 DHM 治疗后,上述作用明显逆转,呈现完全相反的趋势,尤其是用 200mg/kg DHM 治疗后,AD 大鼠的改善更为明显。DHM 通过上调 AMPK/SIRT1 通路抑制炎症反应和海马细胞凋亡,改善认知功能,对 AD 发挥保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b774/6328867/66c751da5c15/bsr-39-bsr20180902-g1.jpg

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