栀子苷对正常和黄疸模型大鼠的亚急性肝、肾毒性  

Effect of Geniposide on Subacute Hepatotoxicity and Nephrotoxicity in Normal and Jaundice Rats

作　　者：张海虹 卫璐戈 李会芳 ZHANG Hai-hong;WEI Lu-ge;LI Hui-fang(Shanxi University of Chinese Medicine,Jinzhong 030619,China)

机构地区：[1]山西中医药大学

出　　处：《中国实验方剂学杂志》2018年第20期140-144,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81573688)

摘　　要：目的：开展栀子苷对正常及黄疸模型大鼠的亚急性肝、肾毒性对比研究,为栀子临床安全用药提供科学依据。方法：SD大鼠80只,随机分为8组,空白组、栀子苷低、中、高剂量（60,180,360 mg·kg^（-1））组,黄疸模型组和α-萘异硫氰酸酯（ANIT）＋栀子苷低、中、高剂量（60,180,360 mg·kg^（-1））组。黄疸模型采用ANIT造模,24 h后灌胃（ig）栀子苷。分别于给药后第7,14天,检测血清丙氨酸氨基转移酶（ALT）,天门冬氨酸氨基转移酶（AST）,总胆红素（TBIL）,尿素氮（BUN）,血肌酐（SCr）活性,取大鼠肝、肾组织进行病理检测。结果：与空白组比较,第7,14天栀子苷中、高剂量组TBIL,SCr明显升高（P〈0.05,P〈0.01）;黄疸模型组大鼠ALT,AST,TBIL均明显升高（P〈0.05,P〈0.01）。与黄疸模型组比,第7,14天ANIT＋栀子苷低、中剂量组AST显著升高（P〈0.01）,ANIT＋栀子苷中剂量组TBIL,BUN明显升高（P〈0.05）。ANIT＋栀子苷高剂量组ig 7 d后陆续全部死亡。病理切片显示,栀子苷给药后肝肾组织出现极轻度炎细胞浸润和肾小管嗜碱性变;模型组和ANIT＋栀子苷各剂量组动物均出现胆管上皮细胞增生,纤维组织增生,并且有随剂量增大病变程度加重的趋势。结论：栀子苷剂量超过180 mg·kg^（-1）（约折合栀子生药量55 g·d^（-1））连续ig给药14 d可对正常及黄疸模型大鼠造成肝、肾损伤;且剂量超过60 mg·kg^（-1）时即会加重黄疸模型大鼠已有的肝损伤,随剂量增加病变程度加重。Objective： To compare the subacute liver and kidney toxicity of geniposide in normal and jaundice rats,and provide a scientific basis for clinical use of gardenia. Method： The 80 SD rats were randomly divided into 8 groups： blank group,normal rats low,medium and high dose administration groups（ 60,180,360 mg·kg^（-1））,jaundice model control group and jaundice model low,medium and high dose administration groups. Jaundice model was induced by α-naphthalene isothiocyanate（ ANIT）,and geniposide was given by intragastric administration after 24 hours. Serum alanine aminotransferase（ ALT）,aspartate aminotransferase（ AST）,total bilirubin（ TBIL）,blood urea nitrogen（ BUN） and creatinine（ SCr） activity were measured on the7 ^（th）day and the 14 ^（th）day after administration. Rat liver and kidney tissues were harvested for pathological examination. Result： Compared with the blank group,TBIL and SCr were significantly increased in the normal rats middle and high dose groups on the 7 ^（th）and 14 ^（th）days（ P〈0. 05,P〈0. 01）; the levels of ALT,AST and TBIL were significantly increased in rats of jaundice model group（ P〈0. 05,P〈0. 01）. Compared with jaundice model group,AST level of jaundice model low and medium dose groups was significantly increased on the 7 ^（th）and14 ^（th）days（ P〈0. 01）,and the TBIL and BUN levels were increased in jaundice model medium dose group（ P〈0. 05）. 7 days after ig administration,all the rats died successively in jaundice model high-dose group. The pathological section showed： after administration in normal rats,very mild inflammatory cell infiltration and basophilic changes in renal tubulars appeared,model control group and jaundice rats in each dose group showed bile duct epithelial hyperplasia,fibrous tissue hyperplasia,and the severity was increased with dose increasing.Conclusion： The ig administration of geniposide at a dose of more than 180 mg·kg^（-1）（ equivalent to about55 g·d^（-1） fo

关 键 词：栀子苷 黄疸模型 亚急性毒性 肝毒性 肾毒性 

分 类 号：R22[医药卫生—中医基础理论] R242[医药卫生—中医学]