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毒液的促凝血作用:动力学建模及丝氨酸蛋白酶活性的作用

Procoagulant Effects of Venom: Kinetic Modeling and Role of Serine Protease Activity.

作者信息

Lopez Gisela L, Nielsen Sarah A, Nielsen Vance G, Fusco Luciano S

机构信息

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Química Básica y Aplicada del Nordeste Argentino (IQUIBA-NEA), Corrientes CP3400, Argentina.

Department of Ecology and Evolutionary Biology, College of Science, University of Arizona, Tucson, AZ 85724, USA.

出版信息

Int J Mol Sci. 2025 Sep 28;26(19):9496. doi: 10.3390/ijms26199496.

DOI:10.3390/ijms26199496
PMID:41096763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12525055/
Abstract

species are responsible for the majority of envenomations in Argentina. In particular, is among the main species responsible for the majority of envenomations in Argentina and causes significant injury and coagulopathy. Given the significance of this venom, the authors sought to define the toxin responsible for coagulopathy with specialized spectrophotometric and thromboelastographic methods. Utilizing clotting time, spectrophotometry, and thromboelastography, it was determined that venom has potent, procoagulant activity in human plasma and buffer milieu. Calcium-dependent and -independent activities consistent with serine protease activity were identified. The activity included both thrombin-generating and thrombin-like enzymatic activity. The venom cleaved the serine protease-specific chromogenic substrate β-Ala-Gly-Arg-p-nitroanilide diacetate, and its activity was inhibited in plasma by antithrombin after addition of heparin. Further, venom exposed in isolation to RuCl, a known inhibitor of serine protease-containing venoms, demonstrated decreased activity in human plasma. In conclusion, the present study contributes to a better understanding of venom and may have implications for the rational design of inhibitors, antivenom formulations, or preclinical models to study venom-induced coagulopathies.

摘要

在阿根廷,某些物种是大多数蛇咬伤中毒事件的罪魁祸首。特别是,[物种名称未给出]是阿根廷大多数蛇咬伤中毒事件的主要元凶之一,会造成严重伤害和凝血功能障碍。鉴于这种毒液的重要性,作者试图用专门的分光光度法和血栓弹性描记法来确定导致凝血功能障碍的毒素。通过使用凝血时间、分光光度法和血栓弹性描记法,确定[物种名称未给出]毒液在人体血浆和缓冲液环境中具有强大的促凝血活性。鉴定出了与丝氨酸蛋白酶活性一致的钙依赖性和非钙依赖性活性。该活性包括凝血酶生成活性和类凝血酶活性。这种毒液能切割丝氨酸蛋白酶特异性生色底物β-丙氨酸-甘氨酸-精氨酸-对硝基苯胺二乙酸盐,在加入肝素后,其活性在血浆中被抗凝血酶抑制。此外,单独暴露于RuCl(一种已知的含丝氨酸蛋白酶毒液的抑制剂)中的毒液,在人体血浆中的活性降低。总之,本研究有助于更好地理解[物种名称未给出]毒液,并可能对研究毒液诱导的凝血功能障碍的抑制剂、抗蛇毒血清制剂或临床前模型的合理设计产生影响。

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Myocardial injury and its association with venom-induced coagulopathy following Bothrops atrox snakebite envenomation.矛头蝮蛇咬伤中毒后心肌损伤及其与毒液诱导的凝血病的关联。
Toxicon. 2025 Apr;258:108312. doi: 10.1016/j.toxicon.2025.108312. Epub 2025 Mar 7.
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The Versatility of Serine Proteases from Brazilian Venom: Their Roles in Snakebites and Drug Discovery.巴西毒液中丝氨酸蛋白酶的多功能性:它们在蛇咬伤和药物发现中的作用。
Biomolecules. 2025 Jan 21;15(2):154. doi: 10.3390/biom15020154.
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Acute kidney injury induced by snakebites in pediatric patients.小儿患者蛇咬伤所致急性肾损伤
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Dermatopathological findings of Bothrops atrox snakebites: A case series in the Brazilian Amazon.矛头蝮蛇咬伤的皮肤病理学发现:巴西亚马逊地区的病例系列
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