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The influence of B55γ on the neuroprotective effect of W026B in t-MCAO mice 被引量:1

B55γ蛋白对t-MCAO模型小鼠中W026B神经保护作用的影响
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摘要 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 W026 B 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 B55γin t-MCAO mice.The results showed that the knockdown of B55γsignificantly suppressed the neuroprotective effect of W026B.Further results showed that the knockdown of PPP2R2C,B55γgene,abolished the effect of W026B on reducing the level of NF-κB p65 in ischemic brain tissue,and knockdown of PPP2R2C also reversed the effect of W026B on decreasing the activity of caspase-3 in ischemic brain tissue.In conclusion,protein B55γmight be an important mediator of the protective effect of W026B.B55γactively 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. 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。
作者 Kexiang Gao Xiaoyan Liu Yuanjun Zhu Ye Liu Yinye Wang 高克祥;刘晓岩;朱元军;刘晔;王银叶(北京大学医学部药学院分子与细胞药理学系,北京100191;北京红惠新医药科技有限公司,北京102600)
出处 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2020年第10期711-718,共8页 中国药学(英文版)
基金 National Natural Science Foundation of China(Grant No.81503060 81573333)。
关键词 Ischemia reperfusion W026B B55γ SIRNA INFLAMMATION APOPTOSIS 缺血再灌注 W026B B55γ siRNA 炎症 凋亡
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