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Effect of proteinase inhibitor on onset and development of local damage by snake envenomation

蛋白酶抑制剂对蛇毒局部损伤发生和发展的影响

基本信息

批准号：
15590370
负责人：
MARUYAMA Masugi
金额：
$ 1.86万
依托单位：
University of Miyazaki (2004-2005)宮崎医科大学 (2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

The aim of the present investigation is to estimate the efficacy, of proteinase inhibitors on treatment of local and systemic damage provoked by snake venom. An intrinsic broad-spectrum proteinase inhibitor, murinoglobulin, was purified from rat plasma employing newly developed rapid and easy purification method. The purified murinoglobulin showed strong inhibitory activity against hemorrhagic and edema forming activities of snake venoms from 5 different genera in Viperidae family. The results showed the possible potential of murinoglobulin as an agent for local treatment of snake envenomation. We also estimated the inhibitory capacity of synthetic metalloproteinase inhibitor, Ilomastat (GM6001) and CaEDTA against snake venom hemorrhagic and coagulation activities. We found that both of compounds inhibited hemorrhagic and coagulation activities of Echis shochureki venom which is the most powerful venom among Viperidae family and hardly inhibited by murinoglobulin. However, local application of CaEDTA and/or Ilomastat failed to inhibit local hemorrhage and systemic coagulopathy if applied those inhibitors 10 min after venom inoculation. In case, the inhibitor was applied one minutes after the envenomation, it showed considerable potential to suppress local hemorrhage and systemic coagulopathy. It is assumed that locally inoculated venom could reach systemic circulation surprisingly fast. It might be the reason for the rather weak potential of proteinase inhibitors. Systemic application of inhibitors as well as local application might be effective on circulating toxins.

本研究的目的是评估蛋白酶抑制剂对蛇毒引起的局部和全身损伤的治疗效果。采用一种新的快速、简便的纯化方法从大鼠血浆中分离纯化了一种内源性广谱蛋白酶抑制剂--鼠胰蛋白酶抑制剂。纯化的鼠蛇毒素对蝰蛇科5个属蛇毒的出血和水肿有较强的抑制活性。结果表明，可能的潜力，murinocellulin作为一种代理，局部治疗蛇毒液。我们还评估了合成金属蛋白酶抑制剂，Ilomastat（GM 6001）和CaEDTA对蛇毒出血和凝血活性的抑制能力。结果表明，这两种化合物均能抑制蝰蛇科最强的蛇毒Echis shochureki蛇毒的出血和凝血活性，而鼠胰蛋白酶几乎不能抑制蛇毒的出血和凝血活性。然而，如果在毒液接种后10分钟应用这些抑制剂，则CaEDTA和/或伊洛马司他的局部应用未能抑制局部出血和全身凝血病。在这种情况下，抑制剂在毒液注入后一分钟应用，它显示出相当大的抑制局部出血和全身凝血功能障碍的潜力。据推测，局部接种的毒液可以惊人地快到达体循环。这可能是蛋白酶抑制剂潜力较弱的原因。抑制剂的全身应用以及局部应用可能对循环毒素有效。