Abstract：
The venoms of Australasian elapid snakes are known to possess coagulant activity, including some with strong procoagulant activity and others with anticoagulant activity, although the latter are less well known. This study investigates the anticoagulant activity of Australasian elapid snake venoms, and whether this activity is neutralised by commercial snake antivenom and varespladib (PLA2 inhibiting agent). Clotting assays were completed for 34 species of Australasian elapids. Antivenom neutralisation assays with tiger snake antivenom (TSAV) were performed on five species to determine if there was cross-neutralisation. Varespladib neutralisation assays were also completed for the same five species. All Pseudechis species venoms had anticoagulant activity, except P. porphyriacus, which was procoagulant. Pseudechis species venoms had similar anticoagulant potency ranging from the most potent P. colletti venom to the least potent P. butleri venom. The three Austrelaps (copperhead) species venoms were the next most potent anticoagulants. Six further snakes, Elapognathus coronatus, Acanthophis pyrrhus, A. antarcticus, Suta suta, Denisonia devisi and D. maculata, had weaker anticoagulant activity, except for D. maculata which had similar anticoagulant activity to Pseudechis species. Tiger Snake Antivenom (1200mU/mL) neutralised the anticoagulant effect of P. australis for concentrations up to 1 mg/mL. TSAV (1200mU/mL) also neutralised P. colletti, D. maculata, A. superbus and A. pyrrhus venoms at their EC50, demonstrating cross neutralisation. Varespladib neutralised the anticoagulant effect of P. australis venom at 5 μM and for venoms of P. colletti, D. maculata, A. superbus and A. pyrrhus. We found anticoagulant activity to be present in six genera of Australasian snakes at low concentrations, which can be completely neutralised by both antivenom and varespladib. Anticoagulant activity in Australian elapid venoms was associated with species possessing high PLA2 activity without procoagulant snake venom serine proteases.
摘要：
已知澳大利亚白斑蛇的毒液具有凝血活性，包括一些具有强的促凝血活性和其他具有抗凝血活性，尽管后者不太为人所知。这项研究调查了澳大利亚蛇毒的抗凝血活性，以及该活性是否被商业蛇毒血清和varespladib（PLA2抑制剂）中和。已完成34种澳大利亚类动物的凝血测定。对五个物种进行了虎蛇蛇毒血清（TSAV）的抗蛇毒血清中和测定，以确定是否存在交叉中和。对于相同的五个物种，也完成了Varespladib中和测定。所有假单胞菌的毒液都有抗凝血活性,除了P.卟啉,是促凝血剂。假单胞菌毒液具有相似的抗凝血效力，从最有效的P.colletti毒液到最不有效的P.butleri毒液。三种Austrelaps（铜头）毒液是第二有效的抗凝剂。还有六条蛇,大头蛇，刺五加,A.南极，Sutasuta,Denisoniadevisi和D.maculata,抗凝血活性较弱，除了与假单胞菌具有相似的抗凝血活性外。虎蛇抗蛇毒血清(1200mU/mL)中和浓度高达1mg/mL的澳大利亚假单胞菌的抗凝血作用。TSAV(1200mU/mL)还中和了P.colletti，D.maculata,A.超级巴士和A.pyrhus毒液的EC50，显示交叉中和。Varespladib中和了5μM的澳大利亚疟原虫毒液的抗凝作用，D.maculata,A.超级巴士和A.pyrhus。我们发现在低浓度的澳大利亚蛇的六个属中存在抗凝血活性，可以被抗蛇毒血清和varespladib完全中和。澳大利亚elapid毒液中的抗凝血活性与具有高PLA2活性而没有促凝血蛇毒丝氨酸蛋白酶的物种有关。
