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ShSPI 抑制体内血栓形成和缺血性脑卒中。

ShSPI Inhibits Thrombosis Formation and Ischemic Stroke In Vivo.

机构信息

Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming 650118, China.

National and Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha 410081, China.

出版信息

Int J Mol Sci. 2024 Aug 19;25(16):9003. doi: 10.3390/ijms25169003.

Abstract

Thrombotic diseases, emerging as a global public health hazard with high mortality and disability rates, pose a significant threat to human health and longevity. Although current antithrombotic therapies are effective in treating these conditions, they often carry a substantial risk of bleeding, highlighting the urgent need for safer therapeutic alternatives. Recent evidence has increasingly pointed to a connection between elastase activity and thrombosis. In the current study, we investigated the antithrombotic effects of ShSPI, an elastase inhibitor peptide derived from the venom of . Results showed that ShSPI significantly attenuated carrageenan-induced thrombosis in vivo. Furthermore, ShSPI effectively inhibited the carrageenan-induced decrease in serum superoxide dismutase (SOD) activity and increase in prothrombin time, fibrinogen level, and endothelial nitric oxide synthase (eNOS) activity. In addition, ShSPI reduced intracerebral thrombosis and improved functional outcomes following ischemic stroke in a transient middle cerebral artery occlusion (tMCAO) mouse model. Collectively, these findings suggest that ShSPI is a promising candidate for the development of novel thrombotic therapies.

摘要

血栓性疾病作为一种具有高死亡率和致残率的全球公共卫生危害,对人类健康和长寿构成了重大威胁。尽管目前的抗血栓治疗在治疗这些疾病方面非常有效,但它们往往伴随着大量出血的风险,这凸显了对更安全治疗方法的迫切需求。最近的证据越来越多地表明弹性蛋白酶活性与血栓形成之间存在关联。在本研究中,我们研究了 ShSPI(一种源自蛇毒的弹性蛋白酶抑制剂肽)的抗血栓作用。结果表明,ShSPI 可显著减轻体内角叉菜胶诱导的血栓形成。此外,ShSPI 可有效抑制角叉菜胶诱导的血清超氧化物歧化酶 (SOD) 活性降低和凝血酶原时间、纤维蛋白原水平和内皮型一氧化氮合酶 (eNOS) 活性升高。此外,ShSPI 可减少大脑中动脉短暂性闭塞 (tMCAO) 小鼠模型中的颅内血栓形成,并改善缺血性中风后的功能结局。综上所述,这些发现表明 ShSPI 是开发新型抗血栓治疗方法的有前途的候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c597/11354536/6e988a0f7250/ijms-25-09003-g001.jpg

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