蟾蜍毒素对H22荷瘤小鼠疗效及毒副作用的实验研究

Inhibition effect of eethanol extract of Chinese toad venom on H22 ascites and solid tumors and its toxicity in mice

目的:探讨醇溶性蟾蜍毒素在小鼠体内对H22肝癌细胞的抑制作用及其毒副作用,为进一步分离纯化蟾酥和开发抗肿瘤新药提供动物实验基础。方法:采用减压蒸馏等方法进一步部分分离纯化乙醇溶解的蟾蜍分泌物原浆,获得醇溶性的蟾蜍毒素混合物(ethanolextractofChinesetoadvenom,EET),分别将其作用于H22实体瘤和腹水瘤小鼠模型,计算肿瘤抑制率和生命延长率,判断疗效;同时通过血生化和病理等检测观察其对各脏器的毒副作用。结果:与对照组比较,5mg/kg和0.5mg/kg的EET对H22荷瘤小鼠实体瘤组织的抑瘤率分别是51.6%和41.2%,t=2.346,P=0.028;t=2.109,P=0.045。对腹水瘤小鼠的生命延长率分别是34.7%和27.7%,t=3.346,P=0.002;t=2.312,P=0.035。同时,0.5mg/kg的EET可明显升高白细胞达(11.6±2.3)×109L-1,t=3.326,P=0.002。但EET在5mg/kg时可引起总胆红素升高达(46.5±14.8)μmol/L,t=2.347,P=0.036。结论:0.5～5mg/kg的EET可以明显抑制荷瘤小鼠体内H22肿瘤细胞的生长,且远远低于华蟾素的有效剂量范围;但EET的剂量达到5mg/kg时可以损伤肝脏。

OBJECTIVE：To study the inhibition effect of ethanol extract of chineve toad venom （EET） on H22 ascites and .solid tumors and its toxicity in mice. METHODS： EET was prepared by decompress stilling and then injected intraperitoneally or subcutaneously into the mice bearing H22 ascites or .solid tumors. The inhibition rates of tumor and the extended rate of life span in mice were calculated and the toxicity of EET was evaluated by biochemical parameters and pathological examination. RESULTS： The inhibition rate of tumor in mice bearing H22 solid tumors were 51.6% （t=2. 346, P=0.028） and 41.2%（t=2. 109, P=0. 045） and the extended rate of life span in mice bearing H22 ascites tumors were 34. 7% （t = 3.346, P=0.002） and 27.7%（t=2.312, P=0.035） in mice receiving EET of 5 mg/kg and 0. 5 mg/kg, respectively. EET of 0. 5 mg/kg increased the number of white blood cells to （11. 6±2.3） × 10^9/L （t=3.326, P=0.002） and EET of 5 mg/kg increased the total bilirubin to （46. 5 ± 14. 8） μmol/L （t=2. 374, P=0. 036）. CONCLUSIONS： The results suggest that EET of 0. 5 to 5 mg/kg could inhibit the growth of H22 ascites and solid tumors in vivo, but EET of 5 mg/kg may injure the liver of mice.