Devaux C, Rochat H
Biochimie-ingénierie des protéines, UMR 6560, CNRS-Université de la Méditerranée, IFR Jean Roche, Faculté de médecine Nord, Bd Pierre Dramard, 13916 Marseille, France.
Bull Soc Pathol Exot. 2002 Aug;95(3):197-9.
Improving the efficacy of envenomation treatment depends on what is known about active molecules present in venoms. Regarding scorpions, studies carried out mainly on the most poisonous species have shown that the toxicity and mortality were due to small proteins-toxins--able to interfere with the normal process of the ionic channels. In certain cases, using the mouse model, it has been shown that over 90% of mortality was due to toxins operating on the sodium channels implicated in the action potential of the excitable cells. Pharmacokinetic studies have shown the diversity of their mode of action implying an adaptation of the means and tools intended to neutralise them. The toxins active on the sodium channels represent a family of proteins from 60 to 65 amino acids linked by 4 disulphide bridges with a very strong antigenic polymorphism; this has certain implications in terms of paraspecificity of antivenoms. The problem is even more complicated when one considers the variation of toxin quantity from one animal to another of the same species. Another approach is to identify the most active and represented toxins in venoms for each antigenic group and to develop a means of neutralizing them. It would also be possible to define toxoids for use either in the production of the antivenoms or as immunological protection for individuals at risk. Lastly, where symptomatic treatment is concerned, certain drugs such as aspirin, quinine or dandrolene have been shown definitely to increase the value of the LD50 in the mouse.
提高蛇毒中毒治疗的疗效取决于对毒液中活性分子的了解。关于蝎子,主要针对最毒种类进行的研究表明,毒性和死亡率是由能够干扰离子通道正常过程的小蛋白质毒素引起的。在某些情况下,利用小鼠模型已表明,超过90%的死亡率是由作用于与可兴奋细胞动作电位相关的钠通道的毒素所致。药代动力学研究表明了它们作用方式的多样性,这意味着需要调整用于中和它们的方法和工具。作用于钠通道的毒素代表了一类由60至65个氨基酸组成的蛋白质家族,通过4个二硫键相连,具有很强的抗原多态性;这在抗蛇毒血清的副特异性方面具有一定影响。当考虑同一物种不同个体之间毒素量的差异时,问题会更加复杂。另一种方法是识别每种抗原组毒液中最具活性且含量最多的毒素,并开发中和它们的方法。也有可能定义类毒素,用于生产抗蛇毒血清或为有风险的个体提供免疫保护。最后,就对症治疗而言,某些药物如阿司匹林、奎宁或丹曲林已被明确证明可提高小鼠的半数致死量值。