肝胆结石片的长期毒性和致突变作用研究  

Study on Mutation Leading Effect and Long-tern Toxicity of Gandan Jieshi Tablets

作　　者：万尧德[1] 万小平[2] 陈淑芬[3] 潭建东 刘小丽[2] 

机构地区：[1]四川省中药研究所,成都市610041 [2]重庆市卫生防疫站,重庆市400042 [3]四川省中医药研究院,成都市610041

出　　处：《中国药房》1999年第6期250-253,共4页China Pharmacy

摘　　要：目的 :观察大鼠长期ig 肝胆结石片后的毒性反应及程度 ,对动物细胞基因有无致突变作用 ,为临床安全用药提供参考。方法 :根据小动物急毒试验结果 ,以肝胆结石片3、6、12g(生药 )/(kg·d) ,并设赋型剂对照组 ,每组40只 ,各组每天ig1次 ,连续180d ,观察用药后大鼠的一般行为、体重、血象、血液生化、系统尸解和病理组织学检查 ,并采用Aems、中国仓鼠CHL细胞染色体畸变、人体外周淋巴细胞畸变、啮齿动物PCE微核试验 ,观察对细胞基因有无影响。结果 :分别ig肝胆结石片3、6、12g(生药 )/(kg·d)是临床公斤体重剂量的34 3倍、68 6倍、137 2倍 ,连续180d ,结果对SD大鼠的一般行为无异常改变 ;大剂量ig 自30d、中小剂量自50d后均有体重增长速度减慢 ,但继续服180d ,各组体重差距无显著变化 ;分别于90d、180d检测各组动物的血液各种指标 ,主要脏器 (系数及组织病理学 )均无不良影响 ,且无延续毒性反应 ;Aems试验结果为阴性 ,对人体外周淋巴细胞染色体无损伤 ,对CHL细胞染色体及小鼠骨髓PCE微核率无增加作用。结论 :连续ig 不同剂量的肝胆结石片180d ,除对大鼠体重增长速度有所抑制外 ,其它未见动物有不良反应 ,无延续性毒性 ,无致突变作用 ,现有临床使用剂量长期服用是安全的。OBJECTIVE:To observe the toxic reaction of long-tern oral administration of Gandan Jieshi tablets (GJ) in rats,and the mutation leading effect of GJ on animal cell gene,to provide reference for clinic safe use of drugs.METHODS:According to the result of acute toxic experiment on little animals,160 rats were classified to 3,6 and 12g/(kg.d) GJ groups and control group,each group 40 rats,every group was orally given once daily and continuously for 180 days.The rat's general behavior,body weight,blood cytology,blood biochemistry,systemic autopsy and histopathological examination were observed after being given GJ,and also applied Aems test, the chromosome distortion test of CHL cell,the chromosome distortion test of human peripheral lymphocyte,the PCG micronucleus test of mice to estimate the influence of the drugs upon cell gene.RESULTS:The dose in 3,6 and 12g/(kg.d) GJ groups during 180 days were 34.3、68.6 and 137.2 times higher than the clinical dosage respectively.The drug had no obvious influence on general behavior of SD rats.Decline in body weight increasing rate was shown after 30 days in large dose group,and also after 50 days in moderate and small dose groups,but the disparity in body weight among groups was not significant when GJ were continuously given until the 180th day.Blood cytology,coefficient of viscera and other parameters were examined at the 90th day and 180th day respectively.The results showed that there were no harmful effects and persistent toxic reaction.The Ames test was negative.The drugs did not damage chromosome of peripheral lymphocyte of human being ,and did not increase the chromosome distortion ratio of DHL cell and the PCE micronucleus ratio of mice marrow cell.CONCLUSION:There are no side effects,persistent toxicity and mutation leading effect,after giving GJ orally in various doses for 180 days consecutively,except the inhibiting of the body weigh increasing rate of rats.It is safe to take present clinical dose for long-term use.

关 键 词：肝胆结石片 毒性 组织病理学 致突变作用 

分 类 号：R975.5[医药卫生—药品]