皖南蝮蛇毒蛋白C激活物的急性毒性作用的研究

目的: 探讨蛇毒蛋白C激活物(protein C activator, PCA)对大、小鼠的急性毒理反应。方法: 大鼠采用上下剂量增减法,小鼠采用半数致死量法,观察实验动物症状、体征、死亡时间和累积死亡率。结果: PCA尾静脉注射大鼠(剂量 17.5~175 mg/kg)、小鼠(剂量为 6.25~11 mg/kg)的中毒表现为不同程度的口鼻泡沫状出血、呼吸困难、心率加快、走路不稳、蜷缩、昏厥性抽搐;大、小鼠尾静脉注射PCA的LD₅₀及其95%可信限分别为 29.57(17.5~55) mg/kg 和 8.05(7.55~8.54) mg/kg;大体解剖可见双肺有片块状出血,病理镜检显示出血主要累及肺泡、支气管等。其他器官未见明显异常。结论: 皖南蝮蛇毒PCA的毒性主要是抗凝过度导致的出血,肺出血引起的急性呼吸衰竭是实验动物死亡主要原因。

Acute toxicity of protein C activator from venom of Agkistrodon halys in rats and mice

AIM: To investigate the acute toxicity of protein C activator from venom of Agkistrodon halys in rats and mice.METHODS: Rats using the up-and-down procedure and mice using median lethal dose; the acute toxical symptoms, signs, death time and accumulated death rate were observed.RESULTS: PCA tail intravenous of rats (dose of 17.5-175 mg/kg), mice (dose of 6.25-11 mg/kg) poisoning in different degree of mouth and nose foam bleeding, dyspnea, heart rate, unstable walking, crouching, consecutive convulsion. The LD₅₀ and its 95%confident limit of PCA to rats and mice were 29.57 (17.5-55) mg/kg and 8.05 (7.55-8.54) mg/kg respectively. A massive hemorrhage was noted in double lung, and pathological examination shows hemorrhage mainly involved in the alveoli, bronchi, etc. Other organs showed no obvious abnormality.CONCLUSION: The main toxicity of PCA from venom of Agkistrodon halys was hemorrhage induced by anticoagulation. In addition, the acute respiratory failure induced by pneumorr- hagia was the major cause for animal death.