中药利胆合剂配方颗粒剂急性毒性实验  

Acute toxicity test of the Li-Dan-He-Ji granules

作　　者：苏梦洁 秦欢 易巍 周俪姗[4] 鄢素琪 Su Mengjie;Qin Huan;Yi Wei;Zhou Lishan;Yan Suqi(Clinical College of Traditional Chinese Medicine,Hubei University of Chinese Medicine,Wuhan 430065,Hubei,China;Department of Clinical Laboratory,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,Hubei,China;Department of Integrated Traditional Chinese and Western Medicine,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,Hubei,China;Department of Gynecology,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430016,Hubei,China)

机构地区：[1]湖北中医药大学中医学院,武汉430065 [2]华中科技大学同济医学院附属武汉儿童医院检验科,湖北武汉430016 [3]华中科技大学同济医学院附属武汉儿童医院中西医结合科,湖北武汉430016 [4]华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)妇科,湖北武汉430016

出　　处：《中华危重病急救医学》2023年第12期1316-1320,共5页Chinese Critical Care Medicine

基　　金：国家自然科学基金面上项目(81574024);湖北省武汉市临床医学科研项目(WZ17A07);湖北省中医药中西医结合科研项目(2017HZ-Y35)。

摘　　要：目的观察中药利胆合剂中药配方颗粒剂的急性毒性反应,并评价其用药安全性。方法采用随机数字表法将60只C57BL6/J小鼠分为正常对照组、溶媒组及给药组,每组雌雄各10只。参照《药物单次给药毒性研究技术指导原则》,采用最大给药量(MAD),给药组灌胃利胆合剂复方颗粒剂0.04 mL/g(42.8 g/kg),24 h内给药3次,每次间隔6 h以上;溶媒组灌服等体积纯净水;正常对照组不予任何处理。连续观察14 d,记录各组小鼠外观特征、行为活动、体质量变化及死亡数;第14天摘眼球取血,检测白细胞计数(WBC)、淋巴细胞计数(LYM)、中性粒细胞计数(NEU)、淋巴细胞比例(LYM%)、中性粒细胞比例(NEU%)、红细胞计数(RBC)、血红蛋白(Hb)、血小板计数(PLT)等血常规指标,以及丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、血尿素氮(BUN)、肌酐(Cr)等生化指标;随后处死小鼠,采用苏木素-伊红(HE)染色观察肝、肾组织病理学改变,并计算心、肝、脾、肺、肾、胸腺等器官指数。结果小鼠灌服利胆合剂复方颗粒剂进行急性毒性预实验,未获得半数致死量(LD_(50)),故采用MAD进行急性毒性实验。MAD实验期间3组动物均无死亡,其行为活动正常,肝肾组织病理学检查无明显改变。溶媒组、给药组与正常对照组比较小鼠体质量、血常规和血生化指标、器官指数等差异均无统计学意义(均P>0.05)。其中正常对照雌雄组、溶媒雌雄组和给药雌雄组的体质量(g)在给药前分别为18.96±1.14、19.65±1.45、19.33±1.30、19.53±1.22、19.28±1.69和19.48±1.28,给药后14 d分别为27.69±0.81、28.19±2.22、27.77±1.00、27.88±1.85、27.92±1.33和28.07±1.93。结论利胆合剂复方颗粒剂口服毒性小,结合临床用药观察,能安全用于婴儿。Objective To observe the acute toxic reaction of the Li-Dan-He-Ji granules,and to evaluate its safety.Methods Sixty C57BL6/J mice were randomly divided into normal control group,vehicle group and drug treatment group,with 10 females and 10 males in each group.According to the Technical guidelines for the study of toxicity of single drug administration,the maximum administration dosage(MAD)was used to intragastric administration of Li-Dan-He-Ji granules 0.04 mL/g(42.8 g/kg),three times within 24 hours,with an interval of 6 hours.The vehicle group was fed with the same pure water.The normal control group received no treatment.The mice were observed continuously for 14 days,and the appearance characteristics,behavioral activities,body weight changes and the number of deaths in each group were recorded.At the 14 days,blood samples were collected from the eyeballs,and routine blood tests such as white blood cell count(WBC),lymphocyte count(LYM),neutrophil count(NEU),lymphocyte percentage(LYM%),neutrophil percentage(NEU%),red blood cell count(RBC),hemoglobin(Hb),and platelet count(PLT)were performed.And alanine aminotransferase(ALT),aspartate aminotransferase(AST),blood urea nitrogen(BUN),creatinine(Cr)and other biochemical indicators.The mice were then sacrificed,and the histopathological changes of liver and kidney were observed by hematoxylin-eosin(HE)staining.The organ indexes of heart,liver,spleen,lung,kidney and thymus were calculated.Results The median lethal dose(LD_(50))of Li-Dan-He-Ji granules were not obtained.During the MAD experiment,the animals in each group did not die,their behavioral activities were normal,and there was no significant change in liver and kidney histopathological examination.There were no significant differences in body weight,blood routine,biochemical indexes and organ index among all groups(all P>0.05).The body weight(g)of normal control female and male group,vehicle female and male group and drug female and male group before administration were 18.96±1.14,19.65±1.45,19.33±1.30,19.

关 键 词：利胆合剂 急性毒性实验 最大给药量 药物安全性 

分 类 号：R285.1[医药卫生—中药学]