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白藜芦醇通过激活 PI3K/Akt 信号通路延迟 6-羟多巴胺诱导的细胞凋亡。

Resveratrol delays 6-hydroxydopamine-induced apoptosis by activating the PI3K/Akt signaling pathway.

机构信息

Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China; Drug Clinical Trial Institution, The First People's Hospital of Zunyi & The Third Affiliated Hospital of Zunyi Medical University, Guizhou, China.

Key Laboratory of Basic Pharmacology and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Guizhou, China.

出版信息

Exp Gerontol. 2019 Sep;124:110653. doi: 10.1016/j.exger.2019.110653. Epub 2019 Jul 8.

Abstract

This study aimed to determine whether resveratrol (Res) delays the progression of 6-hydroxydopamine (6-OHDA)-induced apoptosis via activating the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. Sprague-Dawley (SD) rats were unilaterally injected with 6-OHDA (8 μg/4 μL) into the substantia nigra of the midbrain. Res (15 and 30 mg/kg) was given orally to the rats for a total of 36 days to examine its protective effects. We first tested whether Res can delay the progression of 6-OHDA-induced damage by measuring weight and performance on behavioral tests (rotarod, open field test and grid test) and further explored whether this effect is related to the activation of the PI3K/Akt signaling pathway using immunohistochemistry (IHC) and Western blotting (WB). Our results showed that the damage induced by 6-OHDA gradually worsened, while Res 30 mg/kg treatment significantly improved motor function and increased body weight. Compared with those in the model group, the number of dopaminergic neurons cells and the expression of PI3K-110α, p-Akt Ser473, and pro-caspase-3 in the Res 30 mg/kg group were significantly increased, and the Bax/Bcl-2 ratio and the level of activated caspase-3 was decreased. The results indicate that Res ameliorates 6-OHDA-induced apoptosis and motor dysfunction via activating the PI3K/Akt signaling pathway, delaying the progression of Parkinson's disease (PD) symptoms in this model.

摘要

本研究旨在探讨白藜芦醇(Res)是否通过激活磷脂酰肌醇 3-激酶(PI3K)/蛋白激酶 B(Akt)信号通路来延缓 6-羟多巴胺(6-OHDA)诱导的凋亡进展。Sprague-Dawley(SD)大鼠单侧纹状体中脑注射 6-OHDA(8μg/4μL)。Res(15 和 30mg/kg)经口给予大鼠,共 36 天,以检查其保护作用。我们首先通过测量行为测试(旋转棒、旷场试验和网格试验)中的体重和表现来测试 Res 是否可以延缓 6-OHDA 诱导的损伤进展,进一步通过免疫组织化学(IHC)和 Western blot(WB)探索这种作用是否与 PI3K/Akt 信号通路的激活有关。我们的结果表明,6-OHDA 诱导的损伤逐渐加重,而 Res 30mg/kg 治疗可显著改善运动功能并增加体重。与模型组相比,Res 30mg/kg 组多巴胺能神经元细胞数量增加,PI3K-110α、p-Akt Ser473 和 pro-caspase-3 的表达增加,Bax/Bcl-2 比值和激活的 caspase-3 水平降低。结果表明,Res 通过激活 PI3K/Akt 信号通路改善 6-OHDA 诱导的凋亡和运动功能障碍,延缓该模型帕金森病(PD)症状的进展。

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