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印度洋-太平洋海蛇毒液的体外神经肌肉活性:两种市售抗蛇毒血清的疗效

The in vitro neuromuscular activity of Indo-Pacific sea-snake venoms: efficacy of two commercially available antivenoms.

作者信息

Chetty Navinisha, Du Amanda, Hodgson Wayne C, Winkel Ken, Fry Bryan G

机构信息

Monash Venom Group, Department of Pharmacology, Monash University, Wellington Rd, Clayton, Vic. 3800, Australia.

出版信息

Toxicon. 2004 Aug;44(2):193-200. doi: 10.1016/j.toxicon.2004.05.022.

DOI:10.1016/j.toxicon.2004.05.022
PMID:15246769
Abstract

We examined the neurotoxicity of the following sea snake venoms: Enhydrina schistosa (geographical variants from Weipa and Malaysia), Lapemis curtus (Weipa and Malaysia), Laticauda colubrina, Aipysurus laevis, Aipysurus fuscus and Aipysurus foliosquamatus. Venom from a terrestrial snake, Notechis scutatus (tiger snake), was used as a reference. All venoms (1 and 3 microg/ml) abolished indirect twitches of the chick biventer cervicis muscle and significantly inhibited responses to ACh (1 mM) and CCh (20 microM), but not KCl (40 mM), indicating the presence of post-synaptic toxins. Prior administration (10 min) of CSL sea snake antivenom (1 unit/ml) attenuated the twitch blockade produced by N. scutatus venom and all sea snake venoms (1 microg/ml). Prior administration (10 min) of CSL tiger snake antivenom (1 unit/ml) attenuated the twitch blockade of all venoms except those produced by E. schistosa (Malaysia and Weipa) and A. foliosquamatus. Administration of CSL sea snake antivenom (1 unit/ml) at t90 (i.e. time at which 90% inhibition of initial twitch height occurred) reversed the inhibition of twitches (20-50%) produced by the sea snake venoms (1 microg/ml) but not by N. scutatus venom (1 microg/ml). CSL tiger snake antivenom (1 unit/ml) administered at t90 produced only minor reversal (i.e. 15-25%) of the twitch blockade caused by L. curtus (Weipa), A. foliosquamatus, L. colubrina and A. laevis venoms (1 microg/ml). Differences in the rate of reversal of the neurotoxicity produced by the two geographical variants of E. schistosa venom, after addition of CSL sea snake antivenom, indicate possible differences in venom components. This study shows that sea snake venoms contain potent post-synaptic activity that, despite the significant genetic distances between the lineages, can be neutralised with CSL sea snake antivenom. However, the effects of CSL tiger snake antivenom are more variable.

摘要

我们检测了以下海蛇毒液的神经毒性

裂颏海蛇(来自韦帕和马来西亚的地理变种)、短尾海蛇(韦帕和马来西亚)、扁尾海蛇、平滑剑尾海蛇、棕剑尾海蛇和叶鳞剑尾海蛇。一种陆生蛇——盾鼻蛇(虎蛇)的毒液用作对照。所有毒液(1和3微克/毫升)均可消除雏鸡颈二腹肌的间接抽搐,并显著抑制对乙酰胆碱(1毫摩尔/升)和氯胆碱(20微摩尔/升)的反应,但对氯化钾(40毫摩尔/升)无抑制作用,表明存在突触后毒素。预先给予(10分钟)CSL海蛇抗蛇毒血清(1单位/毫升)可减弱盾鼻蛇毒液和所有海蛇毒液(1微克/毫升)所产生的抽搐阻断作用。预先给予(10分钟)CSL虎蛇抗蛇毒血清(1单位/毫升)可减弱除裂颏海蛇(马来西亚和韦帕)及叶鳞剑尾海蛇毒液外的所有毒液的抽搐阻断作用。在t90(即初始抽搐高度抑制90%的时间点)给予CSL海蛇抗蛇毒血清(1单位/毫升)可逆转海蛇毒液(1微克/毫升)所产生的抽搐抑制作用(20 - 50%),但不能逆转盾鼻蛇毒液(1微克/毫升)所产生的抑制作用。在t90给予CSL虎蛇抗蛇毒血清(1单位/毫升)仅能使短尾海蛇(韦帕)、叶鳞剑尾海蛇、扁尾海蛇和平滑剑尾海蛇毒液(1微克/毫升)所引起的抽搐阻断作用产生轻微逆转(即15 - 25%)。加入CSL海蛇抗蛇毒血清后,裂颏海蛇毒液的两种地理变种所产生的神经毒性逆转速率存在差异,这表明毒液成分可能存在差异。本研究表明,海蛇毒液含有强大的突触后活性,尽管各谱系之间存在显著的遗传距离,但CSL海蛇抗蛇毒血清可将其中和。然而,CSL虎蛇抗蛇毒血清的效果则更具变异性。

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