Envenomings by some populations of the Russell's viper (Daboia russelii) are characterized by a systemic capillary leak syndrome (CLS) which causes hemoconcentration, and is associated with the severity of envenoming. We adapted a model of CLS in mice by assessing hemoconcentration. The venom of D. russelii from Pakistan, but not that of another viperid, Bothrops asper, induced hemoconcentration and an increment in vascular permeability, being devoid of hemorrhagic activity at the doses tested. These findings reveal a dichotomous pattern of vasculotoxicity in viperid snake venoms. This difference might depend on variations in venom composition, especially regarding metalloproteinases (SVMPs), which are low in Pakistani D. russelii and high in B. asper. Inhibition of SVMPs and phospholipases A2 in D. russelii venom did not abrogate hemoconcentration. An hemoconcentration-inducing fraction was obtained by chromatography, which contains vascular endothelial growth factor (VEGF), a known potent inducer of increment in vascular permeability. Exudates collected from tissue injected with venom also induced hemoconcentration, and the effect was inhibited by antivenom. However, the amount of venom in exudate required to induce the effect is low, as compared with venom dissolved in saline solution, hence suggesting that endogenous proteins present in the exudate, probably inflammatory mediators, potentiate the effect.

译文

罗素毒蛇 (Daboia russelii) 的某些人群的毒害特征是引起血液浓缩的全身性毛细血管渗漏综合征 (CLS),并与毒害的严重程度有关。我们通过评估血液浓度来适应小鼠CLS模型。来自巴基斯坦的D. russelii的毒液,而不是另一种viperid Bothrops asper的毒液,会引起血液浓缩和血管通透性增加,在测试剂量下没有出血活性。这些发现揭示了蛇毒液中血管毒性的二分模式。这种差异可能取决于毒液组成的变化,尤其是关于金属蛋白酶 (svmp),巴基斯坦D. russelii低,B. asper高。抑制D. russelii毒液中的SVMPs和磷脂酶A2不会消除血液浓缩。通过色谱法获得血液浓缩诱导级分,其中包含血管内皮生长因子 (VEGF),这是一种已知的有效的血管通透性增加诱导剂。从注射毒液的组织中收集的渗出物也会引起血液浓缩,并且该作用被抗蛇毒血清抑制。然而,与溶解在盐溶液中的毒液相比,诱导作用所需的渗出液中的毒液量较低,因此表明渗出液中存在的内源性蛋白质 (可能是炎症介质) 增强了作用。

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