眼镜蛇毒细胞毒素CTXn的致死毒性及药物依赖性研究  

Studies on lethal toxicity and drug dependence of CTXn from Naja atra venom

作　　者：崔超伟[1] 李春霞[2] 董伟华[1] 孔天翰[1] 

机构地区：[1]广州医学院病理生理教研室,广东广州510182 [2]南方医科大学珠江医院,广东广州510280

出　　处：《蛇志》2010年第2期85-88,96,共5页Journal of Snake

基　　金：广东省自然科学基金资助项目(No.204102537)

摘　　要：目的研究眼镜蛇毒细胞毒素CTXn的致死毒性和药物依赖性,评价其安全性。方法检测CTXn的LD50和对肝细胞色素P450含量的影响,采用大鼠催促戒断模型、自然戒断模型及大鼠条件性位置偏爱模型检测CTXn的药物依赖性。结果 CTXn的LD50为19.61 mg/kg,长期给药对肝细胞色素P450含量无影响。在催促戒断试验中,大鼠连续腹腔注射不同剂量CTXn(0.5、1.0、2.0 mg/kg)10天后经纳洛酮催促,未出现戒断症状及体重下降现象;在大鼠自然戒断试验中,CTXn连续给药21天,停药后大鼠没有出现戒断反应及体重下降现象;在大鼠条件性位置偏爱试验中,CTXn不同剂量组分别连续用药15天后,大鼠在伴药盒的逗留时间均无明显延长,不形成条件性位置偏爱。结论 CTXn毒性较小,长期给药对肝脏药物代谢功能无影响。且不具有身体依赖性及精神依赖性,有潜在的药物开发价值。Objective To investigate the lethal toxicity and drug dependence of CTXn from Naja atra venom and evaluate its drug safety. Methods The LD50of CTXn and the effects of CTXn on cytochrome P450 were detected respectively. Meanwhile, the naloxone precipitated withdrawal test in morphine dependent rats, the spontaneous withdrawal test in rats and the conditioned place preference test in rats were used in this study to detect the dependences of CTXn. Results The LD50 of CTXn in mice was about 19.61 mg/kg. Prolonged administration with CTXn（2.0 mg/kg, i. p. ） did not affect the liver cytochrome P450 contents. In the naloxone precipitated withdrawal tests, after intraperitoneally CTXn at 0.5,1.0,2.0 mg/kg for 10 days continuously, the rats didn＇t show any withdrawal symptoms or the loss of body weight. In the spontaneous withdrawal assay,with the CTXn continuously given for 21 days, the physical signs of withdrawal and the loss of body weight were not found in rats after drug withdrawal. In the conditioned place preference assay, the time of staying in the drug-pair com- partment wasn＇t significantly extended and place preference effect wasn＇t developed in the CTXn treated rats. Conclusion CTXn has the low toxicity and no obvious influence on the function of liver. CTXn doesn＇t induce the physical or psychological dependence in rats in this research,which suggests that CTXn maybe has great potential value for drug exploitation.

关 键 词：CTXn 戒断 身体依赖性 精神依赖性 

分 类 号：R996.3[医药卫生—毒理学]