Snake bite and Venom Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand.
Toxicon. 2011 Sep 1;58(3):230-8. doi: 10.1016/j.toxicon.2011.05.007. Epub 2011 Jun 16.
Acute renal failure (ARF) is the most frequent and a serious complication in victims of Russell's viper snakebites. Russell's viper venom-factor X activator (RVV-X) has been identified as a main procoagulant enzyme involving coagulopathy, which might be responsible for changes in renal hemodynamics and renal functions. Here, we purified RVV-X from crude Russell's viper venom to study renal hemodynamics, renal functions, intravascular clot, and histopathological changes in Sprague-Dawley rats. Changes in renal hemodynamics and renal functions were evaluated by measuring the mean arterial pressure, glomerular filtration rate (GFR), effective renal plasma flow (ERPF), effective renal blood flow (ERBF), renal vascular resistance (RVR), and fractional excretion of electrolytes. After 10 min, rats receiving both crude venom and purified RVV-X decreased GFR, ERPF, and ERBF and increased RVR. These changes correlated to renal lesions. Along with the determination of intravascular clot, rats injected with purified RVV-X increased the average D-dimer level and reached a peak at 10 min, declined temporarily, and then reached another peak at 30 min. The temporal association between clots and renal dysfunction was observed in rats within 10 min after the injection of purified RVV-X. These findings suggested RVV-X as a major cause of renal failure through intravascular clotting in the renal microcirculation.
急性肾衰竭(ARF)是罗素蝰蛇咬伤受害者中最常见且严重的并发症。罗素蝰蛇毒因子 X 激活剂(RVV-X)已被确定为主要的促凝酶,涉及凝血异常,这可能是导致肾血液动力学和肾功能变化的原因。在这里,我们从粗制罗素蝰蛇毒液中纯化 RVV-X,以研究 Sprague-Dawley 大鼠的肾血液动力学、肾功能、血管内血栓形成和组织病理学变化。通过测量平均动脉压、肾小球滤过率(GFR)、有效肾血浆流量(ERPF)、有效肾血流量(ERBF)、肾血管阻力(RVR)和电解质的分数排泄来评估肾血液动力学和肾功能的变化。在 10 分钟后,接受粗制毒液和纯化 RVV-X 的大鼠的 GFR、ERPF 和 ERBF 降低,RVR 增加。这些变化与肾损伤有关。随着血管内血栓形成的测定,注射纯化 RVV-X 的大鼠增加了平均 D-二聚体水平,并在 10 分钟时达到峰值,暂时下降,然后在 30 分钟时再次达到峰值。在注射纯化 RVV-X 后 10 分钟内,观察到大鼠中血栓形成与肾功能障碍之间的时间关联。这些发现表明,RVV-X 通过肾微循环中的血管内血栓形成是导致肾衰竭的主要原因。