中华眼镜蛇(Naja naja atra)毒细胞毒素对动物急性及长期毒性研究

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目的探讨中华眼镜蛇毒中分离纯化的细胞毒素(ChineseCobroVenom-Cytotoxin,CV-CTX)对动物急性及长期毒性的作用。方法急性毒性:小鼠50只,尾静脉一次注入不同剂量的CV-CTX注射液,观察7d内死亡率。犬5只,戊巴比妥钠静脉麻醉后,分别静脉恒速注入不同剂量的CV-CTX,观察5h内血压、心电图及呼吸的变化。长期毒性:大鼠160只分别腹腔注射生理盐水20ml、CV-CTX250,500,1000μg/kg·d-1,连续40d。结果(1)小鼠急性LD50及其95%可信限为1158.7(1070~1254.6)μg/kg,中毒症状呈匍伏、毛松、懒动直到心跳停止,解剖未见重要脏器(心、肺、肝、脾、肾)明显变化。(2)犬静脉恒速注入100μg/kg间隔1h,共5次,呼吸、血压、心电图未见明显变化,一次超过500μg/kg,可使心律不齐而停搏,呼吸停止。(3)大鼠长期毒性实验,3个剂量组,连续用药40d,无一死亡,肝、肾功能及血液生化均无明显影响。病理检查高剂量组部分动物肝脏中度浊肿及水样变性和散在点状坏死,肺有散在性出血;中剂量组肝脏轻度浊肿,偶伴有水样变性,个别动物有小点状坏死,肺有点状出? Objective To investigate the acute and long-term toxicity of ChineseCobroVenom-Cytotoxin (CV-CTX) isolated from cobra venom. Methods Acute toxicity: Fifty mice were injected CV-CTX injection at different doses into the tail vein to observe the mortality within 7 days. Five dogs were anesthetized with pentobarbital sodium, and different doses of CV-CTX were infused intravenously at different rates. The changes of blood pressure, electrocardiogram and respiration were observed within 5 hours. Long-term toxicity: 160 rats were injected intraperitoneally with normal saline 20ml, CV-CTX250, 500,1000μg / kg · d-1 for 40 days. Results (1) The acute LD50 of mice and its 95% confidence limit were 1158.7 (1070 ~ 1254.6) μg / kg. The symptoms of poisoning were creeping, loose hair, lazy movement until the heartbeat stopped. Devices (heart, lung, liver, spleen, kidney) significantly changed. (2) The canine venous injected 100μg / kg at an interval of 1h at a constant speed for 5 times. No significant changes in respiration, blood pressure and electrocardiogram were observed. One time more than 500μg / kg, the cardiac arrhythmia was stopped and the respiration stopped. (3) Long-term toxicity test in rats, three dose groups, continuous medication 40d, no death, liver and kidney function and blood biochemistry had no significant effect. Pathological examination of high-dose group of part of the animal liver moderate turbidity and water-like degeneration and scattered spot necrosis, lung scattered hemorrhage; moderate dose of liver mild turbidity, accompanied by watery degeneration, individual animals have small spots Necrosis, the lung a bit out of shape?
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