芪蟾口服结肠靶向片初步药效学研究

Study of Preliminary Pharmacodynamics on Qichan Targeted Slices

目的:观察芪蟾口服结肠靶向片浸膏对小鼠的急性毒性反应,以评价其安全性;研究芪蟾口服结肠靶向浸膏对H22荷瘤小鼠的抗肿瘤作用。方法:采用经典的急性毒性试验方法测定芪蟾口服结肠靶向浸膏的半数致死量(LD50),观察急性毒性症状,记录死亡数;建立H22荷瘤小鼠模型,随机分成6组,分别给予芪蟾口服结肠靶向浸膏高、中、低剂量灌胃,临床汤剂组灌胃,化疗药物5—Fu腹腔注射单独应用,生理盐水灌胃。正常饲养,给药10天后,摘眼球取血,处死小鼠,分别取出肿瘤组织、小鼠脾脏、胸腺,进行抑瘤率、脾指数、胸腺指数的检测。采用酶联免疫法测定TNF-α、IFN-γ细胞因子水平。结果:芪蟾口服结肠靶向片浸膏小鼠口服LD50为43.26g.kg-1,相当于人临床日用量的19.6倍,;芪蟾口服结肠靶向浸膏各剂量组均可有效抑制肿瘤生长,5-Fu腹腔注射单独应用的抑瘤率为40.52%,芪蟾靶向浸膏3个剂量组的抑瘤率分别为37.41%、33.21%、31.85%。与5-Fu组比较,芪蟾口服结肠靶向浸膏各剂量组能显著提高小鼠脾脏、胸腺的重量(P<0.05)。与模型对照组相比,能明显提高细胞因子TNF-α,IFN-γ的水平(P<0.05)结论:芪蟾靶向浸膏各剂量组均可不同程度抑制肿瘤的生长,以芪蟾靶向浸膏低剂量组效果最为明显,其作用机制与增加小鼠免疫器官重量、增加细胞因子TNF-α,IFN-γ水平等有关。提示芪蟾靶向浸膏有抗肿瘤作用,为临床应用提供科学的实验数据,对临床有实际的指导意义。

Objective：To observe the acute toxicity test of Qichan targeted slices and to provide experimental data for safe use in clinical. To study antitumor activity of Qichan targeted slices on carcinomas. Methods ： The extract of Qichan targeted slices was administrated to mice. The LDs0 was tested by the classical methods of acute toxicity. The acute toxic symptoms was observed, the accumulated death number were recorded. The model of hepatocarcinoma 22 solid tumor - bearing mice produced with Balb/c mice passage in intraperitoneal were randomly divided into 6 groups and treated with the extract of Qichan targeted slices （ low - dose, meta - dose, high - dose）, 5 - Fu respectivel use along and NS. After giving drugs for 10 days, the mice were killed, take out tumor tissue, spleen and thymus were taken out, the inhibiting rate of tumor, the spleen index and thymus index were detected. Murine serum TNF -α and IFN -γ, were detected by ELISA assay. Results： The LD50 of the extract of Qichan targeted slices to mice are 43.26g · kg^-1. They are respectively equal to 19.6 times of the daily dosage in clinical. The extract of Qichan targeted slices can remarkably inhibit the growth rate of tumor, the maximal of which was 37.41%. The spleen lymphocyte stimulation index was significantly increased in treatment groups compared with those of 5 -Fu groups（P 〈 0.05 ）. The leveis of TNF -α and IFN -γ, were significantly increased in treatment groups compared with those of model groups （P 〈 O. 05）. Conclusion： The extract of Qichan targeted slices has good effects on inhibiting tumor growth and enhancing chemotherapy efficacy for tumor - bearing mice. The levels of TNF - α and IFN -γ were increased. These observations give the experimental proof to the clinical of Qichan targeted slices.