太子神悦胶囊给药大鼠180天长期毒性实验研究  

Study on the long-term toxicity of Taizi Shenyue Capsule in rats after 180 days of administration

作　　者：雷帆 胡时先 任宾 邢东明 杨朝竣 王涵斌 陈沫 扎克亚古丽·吾加买提 杜力军 郝娟 Lei Fan;Hu Shixian;Ren Bin;Xing Dongming;Yang Chaojun;Wang Hanbin;Chen Mo;Zakiyagul Gujahmat;Du Lijun;Hao Juan(Laboratory of Pharmaceutical Pharmacology,School of Life Sciences,Tsinghua University,Beijing 100083;Xinjiang Huachun Biopharmaceutical Co.,Ltd.,Urumqi 830000)

机构地区：[1]清华大学生命科学学院药物药理实验室,北京100083 [2]新疆华春生物药业股份有限公司,新疆乌鲁木齐830000

出　　处：《中国现代医药杂志》2024年第11期39-44,共6页Modern Medicine Journal of China

基　　金：国家“重大新药创制”科技重大专项(编号:2018ZX09731-020)。

摘　　要：目的研究太子神悦胶囊灌胃给药180天对大鼠长期毒性的反应和性质。方法采用非近交系封闭群的Wistar大鼠88只,雌雄各半,随机分为阴性(溶媒)对照组、太子神悦胶囊小、中、大剂量共4个试验组,每组22只且雌雄各半。给药组分别经口灌胃给药太子神悦胶囊0.400g/kg、0.828g/kg、1.714g/kg(各相当于临床用量的23、48、100倍),共180天(26周,6个月)。停药后可逆性观察14天(2周)。第180天各组大鼠腹主动脉采血测定血常规、凝血时间及生化指标,给药完毕,每组处死12只大鼠,做尸解和组织学检查,余10只做可逆性观察。取心、肝、脾、肺、肾、胸腺、前列腺、睾丸、附睾、卵巢、子宫、脑称重并计算脏器系数。取心、肝、脾、肺、肾、脑、肾上腺、甲状腺、胸腺、前列腺、睾丸、附睾、卵巢、子宫、胃、十二指肠、胰、主动脉等进行组织学检查。恢复期结束后(第196天)进行相应处理及检测。结果于给药第2周时大剂量组的雄性大鼠相较于对照组,体质量增长值出现了显著下降,差异有统计学意义(P<0.05),并一直持续到给药结束,同时进食量也明显下降(P<0.05)。血液生化结果表明,给药后180天,大、中剂量组尿素(UREA)及肌酐(CRE)低于对照组,差异有统计学意义(P<0.05),但均在正常范围内,无病理学意义。恢复期大、中剂量组大鼠的谷丙转氨酶(ALT)低于对照组,但均在正常范围之内,无病理学意义。对其他血常规指标、血液生化及脏器系数均无明显变化。各剂量组大鼠未见药物中毒所致的病理形态学变化。停药后2周未见药物引起的延迟性毒性反应。结论本次长期毒性实验结果表明太子神悦胶囊1.714g/kg(相当于临床用量的100倍)有一定的非特异性毒性反应,为相对安全剂量范围,0.400g/kg(相当于临床用量的23倍)为绝对安全剂量范围。Objective To investigate the reactions and properties of long-term toxicity of Taizi Shenyue Capsule on rats after 180 days of intragastric administration.Methods A total of 88 Wistar rats(half male and half female),were randomly divided into four experimental groups,including negative(solvent)contrl group and low,medium and high dose of Taizi Shenyue Capsule,with 22 rats in every group(half male and half female),and were administered 0.400g/kg,0.828g/kg and 1.714g/kg of Taizi Shenyue Capsule by oral gavage(equivalent to 23,48 and 100 times of clinical dose,respectively)for a total of 180 days(26 weeks,6 months).After discontinuation,it was reversibly observed for 14 days(2 weeks).On the 180th day,the abdominal aorta blood of rats in the each experimental group was collected to measure blood routine,blood coagulation time and biochemical indexes,and 12 rats were sacrificed in each group after the administration to accept,autopsy and histological examination,and the other 10 rats were observed for reversibility.Heart,liver,spleen,lungs,kidneys,thymus,prostate,testes,epididymis,ovaries,uterus,brain were weighed and organ coefficients were calculated.Histological examination of heart,liver,spleen,lungs,kidneys,brain,adrenal glands,thyroid,thymus,prostate,testes,epididymis,ovaries,uterus,stomach,duodenum,pancreas,aorta and soon were done.After the recovery period(day 196),the corresponding treatment and testing were carried out.Results At the second week of admistration,compared with the control group,the weight growth of male rats in the highdose group decreased significantly(P<0.05),and continued until the end of administration,and the food intake also decreased significantly(P<0.05).The results of blood biochemistry showed that 180 days after administration,the urea(UREA)and creatinine(CRE)levels in the high and medium dose group were lower than those in the control group(P<0.05),but they were within the normal range and had no pathological significance.The alanine aminotransferase(ALT)levels in the convalescent h

关 键 词：太子神悦胶囊 大鼠 长期毒性 

分 类 号：R285.5[医药卫生—中药学]