Batroxobin inhibits astrocyte activation following nigrostriatal pathway injury  

作　　者：Zhuo Zhang Xue Bao Dan Li 

机构地区：[1]Department of Human Anatomy,College of Basic Medical Sciences,China Medical University,Shenyang,Liaoning Province,China

出　　处：《Neural Regeneration Research》2021年第4期721-726,共6页中国神经再生研究（英文版）

基　　金：This study was supported by the National Natural Science Foundation of China,No.81801239(to DL),China Postdoctoral Science Foundation,No.2019M651165(to DL);Doctoral Start-up Foundation of Liaoning Province of China,No.20180540041(to DL).

摘　　要：Batroxobin is a thrombin-like serine protease from the venom of the Bothrops atrox and Bothrops moojeni snake species.Sirtuin 1(Sirt1)has been shown to play an important role in neuroprotection after traumatic brain injury.However,its underlying mechanism of action remains poorly understood.The purpose of this study was to investigate whether the mechanism by which batroxobin participates in the activation of astrocytes is associated with Sirt1.Mouse models of nigrostriatal pathway injury were established.Immediately after modeling,mice were intraperitoneally administered 39 U/kg batroxobin.Batroxobin significantly reduced the expression of cleaved caspase-3 in both the substantia nigra and striatum,inhibited neuronal apoptosis,and promoted the recovery of rat locomotor function.These changes coincided with a remarkable reduction in astrocyte activation.Batroxobin also reduced Sirt1 expression and extracellular signal-regulated kinase activation in brain tissue.Intraperitoneal administration of the Sirt1-specific inhibitor EX527(5 mg/kg)30 minutes prior to injury could inhibit the abovementioned effects.In mouse astrocyte cultures,1 ng/mL batroxobin attenuated interleukin-1β-induced activation of astrocytes and extracellular signal-regulated kinase.EX527 could also inhibit the effects of batroxobin.These findings suggest that batroxobin inhibits astrocyte activation after nigrostriatal pathway injury through the Sirt1 pathway.This study was approved by the Animal Ethics Committee of China Medical University,China(approval No.CMU2020037)on July 19,2015.

关 键 词：ASTROCYTE brain central nervous system factor INJURY PATHWAY 

分 类 号：R453[医药卫生—治疗学] R741[医药卫生—临床医学]