中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 721-726.doi: 10.4103/1673-5374.295343

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

抑制黑质纹状体通路损伤后星形胶质细胞活化的巴曲酶

  

  • 出版日期:2021-04-15 发布日期:2020-12-21
  • 基金资助:

    中国国家自然科学基金项目(81801239),中国博士后科学基金项目(2019M651165),辽宁省博士创业基金项目(20180540041

Batroxobin inhibits astrocyte activation following nigrostriatal pathway injury 

Zhuo Zhang, Xue Bao, Dan Li*   

  1. Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, China
  • Online:2021-04-15 Published:2020-12-21
  • Contact: Dan Li, PhD, dli01@cmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81801239 (to DL), China Postdoctoral Science Foundation, No. 2019M651165 (to DL) and Doctoral Start-up Foundation of Liaoning Province of China, No. 20180540041 (to DL).

摘要:

巴曲酶作为一种与Bothrops atrox蛇毒中纤维蛋白促凝蛋白酶相似的丝氨酸蛋白酶,既往有研究显示,Sirt1在脑损伤后神经保护中具有重要意义,但其潜在的作用机制尚不明确。因此,实验旨在了解巴曲酶参与星形胶质细胞活化的作用机制是否与Sirt1有关。(1)首先制备了小鼠黑质纹状体通路损伤模型,损伤后即刻给予39 U/kg巴曲酶腹腔注射治疗,结果显示,巴曲酶可明显减轻黑质纹状体通路损伤模型小鼠中黑质和纹状体中裂解caspase-3的表达,抑制神经元凋亡,恢复其运动功能,且这些变化与星形细胞活化的降低相吻合,同时巴曲酶还减少了脑组织中Sirt1表达和ERK活化。而损伤前30min腹腔注射Sirt1的特异性抑制剂EX527(5 mg/kg)则能抑制上述现象。(2)在小鼠星形胶质细胞体外模型中,巴曲酶也减弱1 ng/mL白细胞介素1β诱导的星形胶质细胞以及ERK的活化,同时EX527同样可以抑制巴曲酶的作用。(3)结果表明巴曲酶通过Sirt1通路抑制黑质纹状体通路损伤后星形胶质细胞的活化。实验于2015-07-19经中国医科大学动物伦理委员会批准,批准号CMU IACUC 2015038R。

https://orcid.org/0000-0003-0665-2643 (Dan Li) 

关键词: 中枢神经系统, 脑, 损伤, 保护, 星形胶质细胞, 通路, 因子

Abstract: 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. 

Key words: astrocyte, brain, central nervous system, factor, injury, pathway