Triptolide promotes nerve repair after cerebral ischemia reperfusion injury by regulating the NogoA/NgR/ROCK pathway.

IF 1.5 4区 医学 Q4 NEUROSCIENCES
Huiyu Zhang, Minfang Guo, Peijun Zhang, Bingtao Mu, Zhenjun Bai, Liang Li, Jingwen Yu
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引用次数: 0

Abstract

Activation of the NogoA/NgR/ROCK pathway limits nerve repair after brain ischemia-reperfusion (I/R) injury. Triptolide displays anti-inflammatory, anti-oxidant, and immunosuppressive effects and is derived from the traditional Chinese medicine Tripterygium wilfordii Hook F. This agent can also penetrate the blood-brain barrier, where it has a neuroprotective effect and ameliorates cerebral I/R injury via an as yet unknown mechanism(s). Here, an animal model of middle cerebral artery occlusion and reperfusion (MCAO/R) was employed to assess triptolide's therapeutic impact on brain I/R injury and the possible mechanism of action. The results indicate that triptolide treatment can decrease cerebral infarction and nerve injury after cerebral I/R injury. Importantly, in vivo and in vitro experiments revealed that treatment with triptolide decreased NogoA, NgR, p75NTR and ROCK2 expression, and upregulated the expression of GAP43 and PSD-95, thus suggesting improved synaptic function. These results indicate that triptolide can promote nerve repair following brain I/R injury by inhibiting NogoA/NgR/ROCK signalling.

雷公藤内酯通过调节NogoA/NgR/ROCK通路促进脑缺血再灌注损伤后的神经修复
激活 NogoA/NgR/ROCK 通路会限制脑缺血再灌注(I/R)损伤后的神经修复。曲托内酯具有抗炎、抗氧化和免疫抑制作用,是从传统中药Tripterygium wilfordii Hook F中提取的。这种药物还能穿透血脑屏障,在血脑屏障中发挥神经保护作用,并通过一种或多种尚不清楚的机制改善脑缺血再灌注损伤。本文采用大脑中动脉闭塞和再灌注(MCAO/R)动物模型来评估曲普内酯对大脑I/R损伤的治疗作用以及可能的作用机制。结果表明,三苯氧胺能减轻脑I/R损伤后的脑梗死和神经损伤。重要的是,体内和体外实验显示,使用三苯氧胺治疗可降低NogoA、NgR、p75NTR和ROCK2的表达,上调GAP43和PSD-95的表达,从而提示突触功能得到改善。这些结果表明,曲普内酯可通过抑制NogoA/NgR/ROCK信号,促进脑I/R损伤后的神经修复。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Folia neuropathologica
Folia neuropathologica 医学-病理学
CiteScore
2.50
自引率
5.00%
发文量
38
审稿时长
>12 weeks
期刊介绍: Folia Neuropathologica is an official journal of the Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. The journal publishes original articles and reviews that deal with all aspects of clinical and experimental neuropathology and related fields of neuroscience research. The scope of journal includes surgical and experimental pathomorphology, ultrastructure, immunohistochemistry, biochemistry and molecular biology of the nervous tissue. Papers on surgical neuropathology and neuroimaging are also welcome. The reports in other fields relevant to the understanding of human neuropathology might be considered.
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