黄芪、鸡内金复方颗粒剂应用的安全性实验

Experiment on the safety of compound granules of radix astragali and corium stomachium galli

目的:观察以黄芪、鸡内金、神曲等药物组成芪金颗粒剂喂饲大鼠后组织病理、血液生化的多项指标,以探讨芪金颗粒毒理学及安全性。方法:实验于2005-03/2006-01在山西省疾控中心毒理实验室完成。选取清洁级Wistar离乳大鼠80只,随机分为4组,即3个剂量组和阴性对照组,每组20只。3个剂量组(将药物剂量按比例掺入饲料)分别为高剂量组10g/kg(含受试药物100g)、中剂量组5g/kg(含受试药物50g)、低剂量组1.67g/kg(含受试药物16.7g)。各组动物单笼饲养,连续喂养30d。观察和记录动物的一般表现、行为、中毒症状和死亡情况。记录每周体质量,食物摄入量,计算食物利用率。测定血液学指标。测定生化指标。观察肝、脾、肾、睾丸等脏器大体变化,并进行组织病理学切片观察。同时采用Ames试验、小鼠骨髓嗜多染红细胞微核试验、小鼠精子畸形试验等对其进行毒性及安全性评价。结果:在实验过程中无动物死亡,全部进入结果分析。①实验期间各组动物活动正常,各剂量组在体质量增长、进食量和食物利用率方面与对照组比较差异无显著性意义。②各剂量组血液指标和生化指标检测结果与对照组比较差异均无显著性意义。③各剂量组病理组织学方面即肝、脾、肾、胃、肠、睾丸和卵巢均未见特异性病理改变。④Ames试验结果显示,直接作用(-S9)或经代谢活化作用(+S9)均不引起自发回变数增加;未呈现致突变性;小鼠骨髓嗜多染红细胞微核率未发生改变,嗜多染红细胞与正染红细胞的比例大于0.1,未呈现有致突变性;各剂量组精子畸形率与阴性对照组比较差异均无显著性意义意义(P>0.05),而阳性对照组精子畸形率与阴性对照组及各剂量组比较差异有高度显著性(P<0.01),说明芪金颗粒在所设剂量范围内未引起小鼠精子畸形率增高。结论:芪金颗粒对大鼠进食、食物利用率、血液学指标、生化指标、各脏器病理组织学及睾丸卵巢生殖系统等无不良影响,无毒性,具有安全性。

AIM： To evaluate the effect of Qijin granules composed of radix astragali, corium stomachium galli and messa medicata fermentata, etc. histopathological indicators and blood biochemical indicators of rats, and probe into the toxicology and safety of it. METHODS： The experiment was conducted in the Department of Toxicology of Shanxi Provincial Center for Disease Control and Prevention from March 2005 to January 2006. Eighty clean and weaned Wistar rats were randomly divided into 4 groups： high-dose group （10 g/kg, containing 100 g of tested drugs）, middle-dose group （5 g/kg, containing 50 g of tested drugs）, low-dose group （1.67 g/kg, containing 16.7 g of tested drugs） and negative control group with 20 rats in each group. Rats were bred separately for 30 continuous days. The general manifestation, behavior, toxic symptoms and deaths of rats were observed and recorded. The body mass and food-intake were recorded each week and the food using rate were Calculated. The hemat.ological indicators and the biochemical indicators were measured. The general changes in liver, spleen, kidney and didymus etc. were observed, and the pathohistological slices were made. Ames test, marrow polychromatophilic erythrocyte micronucleus test and sperm malformation test, etc. were done to evaluate the toxicology and safety. RESULTS： All animals were involved in the analysis of results, and no one withdrew from the study. ①The behavior of rats were normal in the experiment, and the body mass, food-intake as well as the food using rate of each dose groups did not remarkably differ from the control group. ② There were no significant differences in hematological indicators and biochemical indicators between dose groups and control group. ③No specific pathological change of liver, spleen, kidney, stomach, intestine, didymus and ovaries was found in each dose groups, ④Ames test showed that neither direct action （-S9） nor metabolism activation （＋S9） induced the increase of spontaneity recurring rate, and there were also no induced mutations. The differences in sperm malformation rate among dose groups and control group were not significant （P 〉 0.05）, while the differences in sperm malformation rate between positive control group and all dose groups were greatly remarkable （P 〈 0.01）, which indicate that Qijin granules could not induce the increase of sperm malformation rate in rats at given dose range. CONCLUSION： Qijin granule is safe and has no toxicology and side effects on food-intake, food utilizing rate, hematological indicators, biochemical indicators, pathohistologcal changes, small intestine, intestinal mucosa as well as genital system in rats.