Zhang Zhuo, Bao Xue, Li Dan
Department of Human Anatomy, College of Basic Medical Sciences, China Medical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2021 Apr;16(4):721-726. doi: 10.4103/1673-5374.295343.
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.
巴曲酶是一种来自矛头蝮蛇和莫氏矛头蝮蛇毒液的凝血酶样丝氨酸蛋白酶。沉默调节蛋白1（Sirt1）已被证明在创伤性脑损伤后的神经保护中起重要作用。然而，其潜在的作用机制仍知之甚少。本研究的目的是探讨巴曲酶参与星形胶质细胞激活的机制是否与Sirt1有关。建立黑质纹状体通路损伤的小鼠模型。建模后立即给小鼠腹腔注射39 U/kg巴曲酶。巴曲酶显著降低黑质和纹状体中裂解的半胱天冬酶-3的表达，抑制神经元凋亡，并促进大鼠运动功能的恢复。这些变化与星形胶质细胞激活的显著减少相吻合。巴曲酶还降低了脑组织中Sirt1的表达和细胞外信号调节激酶的激活。在损伤前30分钟腹腔注射Sirt1特异性抑制剂EX527（5 mg/kg）可抑制上述作用。在小鼠星形胶质细胞培养物中，1 ng/mL巴曲酶减弱了白细胞介素-1β诱导的星形胶质细胞激活和细胞外信号调节激酶。EX527也可抑制巴曲酶的作用。这些发现表明，巴曲酶通过Sirt1途径抑制黑质纹状体通路损伤后星形胶质细胞的激活。本研究于2015年7月19日获得中国医科大学动物伦理委员会批准（批准号：CMU2020037）。
