B55γ蛋白对t-MCAO模型小鼠中W026B神经保护作用的影响

doi:10.5246/jcps.2020.10.066

中国药学(英文版) ›› 2020, Vol. 29 ›› Issue (10): 711-718.DOI: 10.5246/jcps.2020.10.066

B55γ蛋白对t-MCAO模型小鼠中W026B神经保护作用的影响

高克祥¹, 刘晓岩¹, 朱元军¹, 刘晔², 王银叶^1*

1. 北京大学医学部药学院分子与细胞药理学系, 北京 100191
2. 北京红惠新医药科技有限公司, 北京 102600

收稿日期:2020-06-24 修回日期:2020-08-15 出版日期:2020-10-31 发布日期:2020-08-30
通讯作者: Tel.: +86-10-82802652, E-mail: wangyinye@bjmu.edu.cn
基金资助:
National Natural Science Foundation of China (Grant No. 81503060, 81573333).

The influence of B55γ on the neuroprotective effect of W026B in t-MCAO mice

Kexiang Gao¹, Xiaoyan Liu¹, Yuanjun Zhu¹, Ye Liu², Yinye Wang^1*

1. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
2. Beijing Honghui New Medical Technology Co. Ltd., Beijing Daxing Biological Medicine Industry Base, Beijing 102600, China

Received:2020-06-24 Revised:2020-08-15 Online:2020-10-31 Published:2020-08-30
Contact: Tel.: +86-10-82802652, E-mail: wangyinye@bjmu.edu.cn
Supported by:
National Natural Science Foundation of China (Grant No. 81503060, 81573333).

摘要/Abstract

摘要：

W026B是一种新合成的木脂素衍生物,已被证明是一种神经保护剂。已有研究表明: W026B可以在不同的模型中显著减少动物脑梗死体积,改善动物行为学评分,并保护血脑屏障,但其发挥保护作用的确切机制仍不清楚。B55γ蛋白是我们前期通过蛋白质组学筛选而得的W026B作用的目标蛋白之一,本研究探究其对t-MCAO小鼠中W026B保护作用的影响。用siRNA PPP2R2C敲低脑组织中B55γ蛋白的表达,以观察B55γ蛋白对W026B作用的影响。结果表明:敲低B55γ蛋白的表达水平可显著抑制W026B的脑保护作用。进一步研究结果显示:敲低B55γ蛋白的表达消除了W026B降低缺血性脑组织中NF-κB p65水平的作用,同时也逆转了W026B降低缺血性脑组织中caspase-3活性的作用。综上所述,蛋白B55γ可能是W026B发挥脑保护作用的重要调节因子, B55γ可通过影响缺血再灌注过程中的炎症反应和凋亡途径密切参与W026B的脑保护作用。这些结果揭示了W026B的神经保护作用的新机制。

关键词: 缺血再灌注, W026B, B55γ, siRNA, 炎症, 凋亡

Abstract:

As a newly synthesized lignan derivative, W026B has been proved to be a neuroprotective agent, and it can significantly reduce cerebral infarct volume, improve behavioral scores and protect blood brain barrier in different models. However, its exact mechanism is still unclear. In the present study, a protein named B55γ, one of candidate targets of W026B screened by proteomic study, was investigated to explore its influence on the effect of W026B in t-MCAO mice. siRNA PPP2R2C was used to knockdown the expression of protein B55γ in t-MCAO mice. The results showed that the knockdown of B55γ significantly suppressed the neuroprotective effect of W026B. Further results showed that the knockdown of PPP2R2C, B55γ gene, abolished the effect of W026B on reducing the level of NF-κB p65 in ischemic brain tissue, and knockdownof PPP2R2C also reversed the effect of W026B on decreasing the activity of caspase-3 in ischemic brain tissue.In conclusion, protein B55γ might be an important mediator of the protective effect of W026B. B55γ actively participated in the brain protective effect of W026B by affecting the inflammatory response and apoptotic pathway during ischemia reperfusion. These results revealed a new mechanism underlying the neuroprotective effect of W026B.

Key words: Ischemia reperfusion, W026B, B55γ, siRNA, Inflammation, Apoptosis

中图分类号:

R963

Supporting:

高克祥, 刘晓岩, 朱元军, 刘晔, 王银叶. B55γ蛋白对t-MCAO模型小鼠中W026B神经保护作用的影响[J]. 中国药学(英文版), 2020, 29(10): 711-718.

Kexiang Gao, Xiaoyan Liu, Yuanjun Zhu, Ye Liu, Yinye Wang. The influence of B55γ on the neuroprotective effect of W026B in t-MCAO mice[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(10): 711-718.

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B55γ蛋白对t-MCAO模型小鼠中W026B神经保护作用的影响

The influence of B55γ on the neuroprotective effect of W026B in t-MCAO mice

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