摘要
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 find out the acute and long-term toxicities of purified CV-CTX from Chinese cobra venom in mice,Methods Fifty mice were divided into five groups,each given different dose of CV-CTX iv, The death rate was estimated within 7 day.Five dogs were given different doses of CV-CTX iv after anaesthetized with sodium pentobarbital.The blood pressure,ECG,respiratory rate were recorded at 10￣30 min interval.One hundred and sixty rats (same number for both sexes)were divided into four groups.One group received ip 0.9% NaCl 20 ml /kg·d-1 as control,the another three groups received ip CV-CTX 250,500,1000μg/kg·d-1 respectively for 40 days continuously.Results The LD50 and 95% confidence limits of CV-CTX in mice was 1158. 7(1070￣1254. 6)μg/kg. After administration the mice decreased their spontaneous movements and some died within 6 hrs. In dogs received iv CVCTX 100 μg/kg every hour for five times no change in blood pressue.Dose which larger than 500 μg/kg caused cardiac arrhythmia and heart arrest.The liver and renal functions as well as biochemical assays of blood were in normal range in all rats after CV-CTX ip 40 days; Pathomorphological examination showed that 4 and 3 rats in the high dose group appeared liver focal necrosis and dispersive lung haemorrhage respectively. But in median dose group only mild cloudy swelling in liver cells and focal haemorrhage in lung were observed.All the pathological changes disappeared when CV-CTX had discontinued after 30 days,Conclusion The toxicity of long-term CV-CTX administration appeared only in the liver and lung,but these toxic changes were reversible.It is suggested that CV-CTX may be prepared as a drug for clinical use.
