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表没食子儿茶素没食子酸酯对帕金森病大鼠黑质神经元凋亡及mTOR/AKT/GSK-3β信号通路的影响及其机制

Effects and mechanism of epigallocatechin-3-gallate on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in Parkinson rats.

作者信息

Zhou Wei, Chen Lei, Hu Xiqing, Cao Shanshan, Yang Junxiu

机构信息

Department of Neurology, Tianjin United Medical Centre.

Tianjin Huanhu Hospital, Tianjin, China.

出版信息

Neuroreport. 2019 Jan 16;30(2):60-65. doi: 10.1097/WNR.0000000000001149.

Abstract

The aim of this study is to investigate the protective effect of epigallocatechin-3-gallate (EGCG) on apoptosis and mTOR/AKT/GSK-3β pathway in substantia nigra neurons in 6-dopamine-induced Parkinson rats. A total of 30 healthy male SD rats were randomly divided into control group, the Parkinson model group, and Parkinson model+EGCG treatment group. The model and EGCG groups were injected into the right striatum with 6-OHDA to establish the Parkinson model, and the control group was injected with saline only. The EGCG group was intragastrically administered with EGCG 50 mg/kg daily for 4 weeks. The rats' turns, speed, and left forelimb usage; neuron apoptosis by TUNEL; and the α-synuclein protein expression in substantia nigra by immunohistochemical staining were studied. Western blotting was used to detect the relative protein (mTOR, AKT and GSK-3β) expressions. Compared with the model group, the EGCG group significantly reduced the rotation speed; increased the left forelimb usage (P<0.01); reduced the neuron apoptosis (P<0.01); decreased α-synuclein expression (P<0.01); and decreased the mTOR, AKT, and GSK-3β protein expressions (P<0.01). EGCG can reduce neuron cell apoptosis in substantia nigra neurons in 6-OHDA-induced Parkinson rats. The mechanism might be related to mTOR/AKT/GSK-3β activation.

摘要

本研究旨在探讨表没食子儿茶素-3-没食子酸酯(EGCG)对6-羟基多巴胺诱导的帕金森病大鼠黑质神经元凋亡及mTOR/AKT/GSK-3β信号通路的保护作用。将30只健康雄性SD大鼠随机分为对照组、帕金森病模型组和帕金森病模型+EGCG治疗组。模型组和EGCG组经右侧纹状体注射6-羟基多巴胺建立帕金森病模型,对照组仅注射生理盐水。EGCG组每天灌胃给予50 mg/kg EGCG,持续4周。观察大鼠的旋转次数、速度和左前肢使用情况;采用TUNEL法检测神经元凋亡;通过免疫组织化学染色检测黑质中α-突触核蛋白的表达。采用蛋白质印迹法检测相关蛋白(mTOR、AKT和GSK-3β)的表达。与模型组相比,EGCG组显著降低了旋转速度;增加了左前肢使用次数(P<0.01);减少了神经元凋亡(P<0.01);降低了α-突触核蛋白表达(P<0.01);降低了mTOR、AKT和GSK-3β蛋白表达(P<0.01)。EGCG可减少6-羟基多巴胺诱导的帕金森病大鼠黑质神经元细胞凋亡。其机制可能与激活mTOR/AKT/GSK-3β信号通路有关。

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