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棕黑锦蛇、赤峰锦蛇和红脖颈槽蛇蛇毒的止血和毒素多样性。

Hemostatic and toxinological diversities in venom of Micrurus tener tener, Micrurus fulvius fulvius and Micrurus isozonus coral snakes.

机构信息

Laboratorio de Fisiopatología, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas (IVIC), Apartado 20632, Caracas 1020A, Venezuela.

出版信息

Toxicon. 2011 Jul;58(1):35-45. doi: 10.1016/j.toxicon.2011.04.020. Epub 2011 May 8.

Abstract

The coral snake Micrurus tener tener (Mtt) from the Elapidae family inhabits the southwestern United States and produces severe cases of envenomations. Although the majority of Mtt venom components are neurotoxins and phospholipase A₂s, this study demonstrated, by SDS-PAGE and molecular exclusion chromatography (MEC), that these venoms also contain high-molecular-weight proteins between 50 and 150 kDa that target the hemostatic system. The biological aspects of other Micrurus venoms were also studied, such as the LD₅₀s of Micrurus isozonus (from 0.52 to 0.61 mg/kg). A pool from these venoms presented a LD₅₀ of 0.57 mg/kg, Micrurus f. fulvius (Mff) and Mtt had LD₅₀s of 0.32 and 0.78 mg/kg, respectively. These venoms contained fibrino(geno)lytic activity, they inhibited platelet aggregation, as well as factor Xa and/or plasmin-like activities. M. isozonus venoms from different Venezuelan geographical regions inhibited ADP-induced platelet aggregation (from 50 to 68%). Micrurus tener tener venom from the United States was the most active with a 95.2% inhibitory effect. This venom showed thrombin-like activity on fibrinogen and human plasma. Fractions of Mtt showed fibrino(geno)lytic activity and inhibition on plasmin amidolytic activity. Several fractions degraded the fibrinogen Aα chains, and fractions F2 and F7 completely degraded both fibrinogen Aα and Bβ chains. To our knowledge, this is the first report on thrombin-like and fibrino(geno)lytic activity and plasmin or factor Xa inhibitors described in Micrurus venoms. Further purification and characterization of these Micrurus venom components could be of therapeutic use in the treatment of hemostatic disorders.

摘要

来自眼镜蛇科的珊瑚蛇 Micrurus tener tener(Mtt)栖息在美国西南部,产生严重的中毒病例。尽管 Mtt 毒液的大多数成分是神经毒素和磷脂酶 A₂,但这项研究通过 SDS-PAGE 和分子排阻层析(MEC)表明,这些毒液还含有分子量在 50 到 150 kDa 之间的高分子量蛋白质,这些蛋白质靶向止血系统。还研究了其他 Micrurus 毒液的生物学方面,例如 Micrurus isozonus 的 LD₅₀(从 0.52 到 0.61 mg/kg)。这些毒液的混合物的 LD₅₀ 为 0.57 mg/kg,Micrurus f. fulvius(Mff)和 Mtt 的 LD₅₀ 分别为 0.32 和 0.78 mg/kg。这些毒液具有纤维蛋白(原)溶解活性,可抑制血小板聚集,以及抑制因子 Xa 和/或纤溶酶样活性。来自委内瑞拉不同地理区域的 M. isozonus 毒液抑制 ADP 诱导的血小板聚集(从 50 到 68%)。来自美国的 Micrurus tener tener 毒液最为活跃,抑制率为 95.2%。这种毒液对纤维蛋白原和人血浆具有类凝血酶活性。Mtt 的几个馏分显示纤维蛋白(原)溶解活性和对纤溶酶 amidolytic 活性的抑制作用。几个馏分降解纤维蛋白原 Aα 链,而馏分 F2 和 F7 完全降解纤维蛋白原 Aα 和 Bβ 链。据我们所知,这是首次在 Micrurus 毒液中报道类凝血酶和纤维蛋白(原)溶解活性以及纤溶酶或因子 Xa 抑制剂。这些 Micrurus 毒液成分的进一步纯化和表征可能在治疗止血障碍方面具有治疗用途。

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