反式阿魏酸-4-β-葡萄糖苷的毒性研究  

Toxicity study of trans-ferulic acid-4-β-glucoside

作　　者：谭玉婷 杨雨琦 李乐 夏童超 兰轲[1] 包旭[1] 杨俊毅[1] TAN Yuting;YANG Yuqi;LI Le;XIA Tongchao;LAN Ke;BAO Xu;YANG Junyi(Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry,Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial Technology,West China School of Pharmacy,Sichuan University,Chengdu,Sichuan,610041 P.R.China;West China School of Medicine,Sichuan University,Chengdu,Sichuan,610041 P.R.China;Xinqiao Hospital,Army Medical University,Chongqing,400037 P.R.China)

机构地区：[1]四川大学华西药学院靶向药物与释药系统教育部重点实验室,四川省植物来源工程实验室和四川省小分子药物精准化工程技术研究中心,四川成都610041 [2]四川大学华西临床医学院,四川成都610041 [3]陆军军医大学第二附属医院,重庆400037

出　　处：《华西药学杂志》2022年第5期523-526,共4页West China Journal of Pharmaceutical Sciences

摘　　要：目的 初步评价反式阿魏酸-4-β-葡萄糖苷(FAG)的安全性。方法 单次给药毒性试验采用最大耐受量法,观察给予药物后动物的毒性反应。重复给药毒性试验将大鼠随机分为对照组和0.5、1、2 g·kg^(-1)剂量组,连续灌胃给药28 d,停药恢复28 d,观察记录大鼠的外观体征、体重、摄食量和各项毒理学指标。结果 单次给药毒性试验结果显示:小鼠灌胃给予8 g·kg^(-1)FAG可引起雄性小鼠体重增长缓慢,但可恢复;灌胃给予4 g·kg^(-1)FAG对大鼠无明显毒性反应。重复给药毒性试验结果显示:高剂量组大鼠出现体重增加和体脂升高,血液学指标出现不同程度的异常改变;低、中、高剂量组的肝脏器指数均明显升高;高剂量组的肾小管管型病变显著增多,以上异常改变停药后均可恢复。结论 FAG小鼠和大鼠单次给药的最大耐受量分别为8、4 g·kg^(-1),约相当于起效剂量的29.6、20.8倍;重复给药试验未见明显毒性反应剂量为0.5 g·kg^(-1)。FAG在临床应用时应重点监测体重、血脂、血液学相关指标及肝、肾功能的变化。OBJECTIVE To preliminarily evaluate the safety of trans-ferulic acid-4-β-glucoside(FAG).METHODS In single dose toxicity study, maximum tolerance dose method was applied to observe the toxic response of the test animals.In the repeated dose toxicity study, rats were randomly divided into control group and 0.5,1,2 g·kg^(-1)groups.All rats were administered by gavage for 28 days followed by 28-day recovery.The general symptoms, body weight, food consumption and various toxicological indexes were detected.RESULTS The result of single dose toxicity study showed that 8 g·kg^(-1)FAG given by gavage to mice caused slow weight gain in males, but could be restored.There is no obvious toxic reaction was observed in rats after intragastric administration of 4 g·kg^(-1)FAG.In repeated-dose toxicity study, following adverse effects were observed in rats at 2 g·kg^(-1):the body weight and body fat increased, and abnormal changes in hematological parameters.The liver organ index was significantly increased in the low, middle and high dose groups;the tubular lesions of renal tubules were significantly increased in the high dose group, and all the above abnormal changes could be recovered after 28-day recovery.CONCLUSION The maximum tolerance dose of FAG in mice and rats by single dose was 8 g·kg^(-1)and 4 g·kg^(-1),about 29.6 times and 20.8 times of clinical dose.The unobserved adverse effect level in repeated doses toxicity study was 0.5 g·kg^(-1).Clinical applications of FAG should focus on monitoring changes in body weight, blood lipid, hematology indicators, liver and kidney function.

关 键 词：附子 反式阿魏酸-4-β-葡萄糖苷 单次给药毒性 重复给药毒性 无毒反应剂量 肝脏器指数 肾小管管型病变 安全性评价 

分 类 号：R96[医药卫生—药理学]