Batroxobin inhibits astrocyte activation following nigrostriatal pathway injury.
Batroxobin inhibits astrocyte activation following nigrostriatal pathway injury.
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巴曲酶抑制黑质纹状体通路损伤后的星形胶质细胞活化
DOI：
10.4103/1673-5374.295343
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发表时间：
2021-04
影响因子：
6.1
通讯作者：
Li D
中科院分区：
文献类型：
--
作者：
Zhang Z;Bao X;Li D
巴曲酶是一种凝血酶样丝氨酸蛋白酶，来自Bothrops atrox和Bothrops moojeni蛇类的毒液。Sirtuin 1（Sirt 1）在创伤性脑损伤后的神经保护中发挥重要作用。然而，其潜在的作用机制仍然知之甚少。本研究旨在探讨巴曲酶参与星形胶质细胞活化的机制是否与Sirt 1有关。建立小鼠黑质纹状体通路损伤模型。模型建立后立即腹腔注射巴曲酶39 U/kg。巴曲酶可明显降低黑质和纹状体中切割的半胱天冬酶-3的表达，抑制神经元凋亡，促进大鼠运动功能的恢复。这些变化与星形胶质细胞活化的显著减少相吻合。巴曲酶还降低了脑组织中Sirt 1的表达和细胞外信号调节激酶的激活。在损伤前30分钟腹腔内给予Sirt 1特异性抑制剂EX 527（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巴曲酶减弱白细胞介素-1 β诱导的星形胶质细胞和细胞外信号调节激酶的活化。EX 527也能抑制巴曲酶的作用。这些结果表明，巴曲酶抑制黑质纹状体通路损伤后星形胶质细胞的激活通过Sirt 1途径。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CMU 2020037）。
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.
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影响因子：
3.3
作者：
Della-Morte, D.;Dave, K. R.;Defazio, R. A.;Bao, Y. C.;Raval, A. P.;Perez-Pinzon, M. A.
通讯作者：
Perez-Pinzon, M. A.
影响因子：
2.1
作者：
Chong ZZ;Maiese K
通讯作者：
Maiese K
DOI：
10.3961/jpmph.2011.44.5.210
发表时间：
2011-09
期刊：
Journal of preventive medicine and public health = Yebang Uihakhoe chi
影响因子：
--
作者：
Khuwaja AK;Khawaja S;Motwani K;Khoja AA;Azam IS;Fatmi Z;Ali BS;Kadir MM
通讯作者：
Kadir MM
影响因子：
10.3
作者：
Chang, Hung-Ming;Wu, Un-In;Lan, Chyn-Tair
通讯作者：
Lan, Chyn-Tair
影响因子：
3.5
作者：
Sakamoto, J;Miura, T;Horio, Y
通讯作者：
Horio, Y