栀子提取物对正常和黄疸模型大鼠慢性肝肾毒性对比研究  

Study on chronic hepatic and renal toxicity of gardenia extract in normal and jaundice model rats

作　　者：李会芳 张海虹 郎霞 LI Hui-fang;ZHANG Hai-hong;LANG Xia(Institute of Pharmaceutical and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi Province,China)

机构地区：[1]山西中医药大学中药与食品工程学院,山西晋中030619

出　　处：《中国临床药理学杂志》2020年第22期3755-3759,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81573688)。

摘　　要：目的比较栀子提取物对正常及黄疸模型大鼠重复给药4周的肝肾毒性差异。方法将192只SD大鼠随机分为8组(空白组、模型组和低、中、高剂量对照组以及低、中、高剂量实验组)。模型组及低、中、高剂量实验组采用α-萘异硫氰酸酯(ANIT) 60 mg·kg^-1灌胃造模,并于第3天起给予ANIT 20 mg·kg^-1灌胃维持模型至第28天。造模24 h后,低、中、高剂量对照组及低、中、高剂量实验组均灌胃相应剂量栀子提取物(剂量分别为0.14,0.28,0.56 g·kg^-1),连续给药28天,停药观察2周。分别于给药后第14,28和42天,检测血清碱性磷酸酶(ALP)、谷丙转氨酶(GPT)、谷草转氨酶(GOT)、总胆红素(TBIL)、尿素氮(BUN)、血清肌酸酐(CREA)活性,取大鼠肝、肾组织进行病理检测。结果给药14 d,中、高剂量实验组大鼠ALP、GPT、TBIL和BUN均明显升高,高剂量对照组大鼠BUN明显升高;给药28 d,高剂量对照组TBIL和BUN均明显升高,低剂量实验组大鼠ALP和GPT均显著升高,中剂量实验组GOT和TBIL均显著升高,停药观察2周之后,各组大鼠肝肾指标差异均无统计学意义(均P>0.05)。结论栀子提取物大剂量连续使用可对正常及黄疸模型大鼠造成肝肾损伤,且对黄疸模型大鼠造成损伤的剂量和时间低于正常大鼠,黄疸模型提高了栀子肝肾毒性的易感性。Objective To compare the hepatorenal toxicity of gardenia jasminoides extract in normal and jaundice rats after repeated administration for 4 weeks. Methods A total of 192 SD rats were randomly divided into 8 groups(blank group, model group, control-L,-M,-H groups and experimental-L,-M,-H groups).The model group and the experimental-L,-M,-H groups were given 60 mg·kg^-1 α-naphthalene isothiocyanate(ANIT) by gavage, and ANIT 20 mg·kg-1 was given for 28 days from the 3 rd day by gavage.After 24 h of modeling, control group and experimental group were given the corresponding doses of gardenia jasminoides extract(0.14, 0.28, 0.56 g·kg^-1, respectively) by gavage. The drugs were administered continuously for 28 days and stopped for 2 weeks.Serum alkaline phosphatase(ALP), glutamic-pyruvic transaminase(GPT), glutamic-oxaloacetic transaminase(GOT), total bilirubin(TBIL), urea nitrogen(BUN) and serum creatinine(CREA) activities were detected on the 14 th,28 th and 42 nd day after administration,respectively. Liver and kidney tissues of rats were taken for pathological examination. Results On 14 days,ALP,GPT,TBIL and BUN in the experimental-M,-H groups were significantly increased,while BUN in the control-H group was significantly increased. After 28 days of administration,TBIL and BUN in the control group-H were significantly increased,ALP and GPT in the experimental-L group were significantly increased,GOT and TBIL in the experimental-M group were significantly increased,and liver and kidney indexes in each group were not statistically different after 2 weeks of withdrawal observation. Conclusion High dose continuous use of gardenia fruit extract can cause liver and kidney injury in normal and jaundice models,and the dose and time of injury in jaundice model rats were lower than those in normal rats,and the jaundice model increased the susceptibility of gardenia jasminoides to hepatotoxicity and nephrotoxicity.

关 键 词：栀子提取物 黄疸模型 肝毒性 肾毒性 

分 类 号：R28[医药卫生—中药学]