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一种作用于钠通道的蝎神经毒素对小鼠神经系统早期发育的毒性作用。

Toxicity during early development of the mouse nervous system of a scorpion neurotoxin active on sodium channels.

作者信息

Clot-Faybesse O, Guieu R, Rochat H, Devaux C

机构信息

Ingénierie des Protéines, CNRS UMR 6560, IFR Jean Roche, Faculté de Médecine-Nord, Univ Mediterranee, Marseille, France.

出版信息

Life Sci. 2000;66(3):185-92. doi: 10.1016/s0024-3205(99)00579-2.

DOI:10.1016/s0024-3205(99)00579-2
PMID:10665992
Abstract

The lethal effects of scorpion envenomation is due to neurotoxins active on voltage-sensitive sodium channels. Dysfunctions of the peripheral and central nervous systems with neurological manifestations are commonly observed after scorpion stings, specially in young children. Since the neurotoxicity of venom fraction is greatly higher by intracerebroventricular than by subcutaneous injections, a direct effect of venom on CNS cannot be excluded specially in infants where the blood-brain barrier is not fully functional. We investigated the activity of a neurotoxin from the scorpion Androctonus australis hector (AahII) in newborn mice at 3, 7 and 14 days after birth and in adults. Young mice (P3, P7) were more sensitive to AahII injected subcutaneously than were adults, but were less sensitive to intracerebroventricular injection. The affinity of AahII for its receptor site on brain synaptosomes from P3 and P7 mice was slightly higher and the density of the binding sites was half that of adult mice. After subcutaneous injection of [125I]-AahII it was also observed that a small amount of radioactivity was found in brains of neonate mice but not in that of adults. This amount is however extremely lower than the value of the LD50 determined by intracerebroventricular injection. Results are consistent with a peripheral action of AahII and show that its toxic activity changes during the mouse nervous system development.

摘要

蝎毒中毒的致死作用归因于对电压敏感性钠通道有活性的神经毒素。蝎螫伤后,尤其是在幼儿中,常观察到伴有神经学表现的外周和中枢神经系统功能障碍。由于毒液组分的神经毒性经脑室内注射比皮下注射要高得多,所以不能排除毒液对中枢神经系统有直接作用,特别是在血脑屏障尚未完全发挥功能的婴儿中。我们研究了来自澳链尾蝎(Androctonus australis hector)的一种神经毒素(AahII)在新生小鼠出生后3天、7天和14天以及成年小鼠中的活性。幼鼠(出生后3天、7天)皮下注射AahII比成年鼠更敏感,但对脑室内注射的敏感性较低。AahII对出生后3天和7天小鼠脑突触体上其受体位点的亲和力略高,且结合位点的密度是成年小鼠的一半。皮下注射[125I]-AahII后还观察到,新生小鼠脑中发现少量放射性,而成年小鼠脑中未发现。然而,这一量远低于经脑室内注射测定的半数致死量值。结果与AahII的外周作用一致,并表明其毒性活性在小鼠神经系统发育过程中发生变化。

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