基于黄疸模型大鼠的栀子苷急性肝肾毒性研究

Acute Hepatotoxicity and Nephrotoxicity Study of Geniposide on Jaundice Rats

目的：观察栀子苷对α-萘异硫氰酸酯（ANIT）所致黄疸模型大鼠的肝肾毒性作用，为栀子的临床安全用药提供参考。方法：Wistar大鼠190只，雌雄各半，随机分为空白组，模型不同时间组，栀子苷不同时间组，其中模型组和栀子甘绀又分为0.5，1，2，4，8，12，24，48，72h组，每组10只，模型组及栀子苷组采用ANIT（60mg·kg^-1）ig一次造模，造模后24h，栀子苷组灌以栀子苷（1.2g·kg^-1），模型组灌以同体积生理盐水。给药后模型组及栀子苷组分别在0.5，1，2，4，8，12，24，48，72h对大鼠眼眶取血，离心获得血清，全自动生化仪测定丙氨酸氨基转移酶（ALT），天冬氨酸氨基转移酶（AST），碱性磷酸酶（ALP），总胆红素（TBIL），血尿素氮（BUN），肌酐（CREA），取肝、肾组织进行病理检查。结果：与空白组比较，给予ANIT后，模型组及栀子苷组在8-72h后ALP，ALT，AST，TBIL肝功能指标不同程度升高（P〈0.05，P〈0.01）；与模型组同时间点比较，栀子苷组在给予栀子苷48，72h后血清中各项ALP，ALT，AST，TBIL肝功能指标显著升高（P〈0，05，P〈0，01），在给药24，48，72h后BUN，CREA显著升高（P〈0.01）；光镜下观察，栀子苷组及模型组不同时间点均出现不同程度的肝脏病理损伤，其巾栀子苷组48，72h肝脏病理损伤较模型组严重，模型组各时间点肾脏病理检查未见异常，而给药后24-72h出现不同程度的。肾脏病理损伤，其中以48h最为严重。结论：栀子苷对ANIT黄疸模型大鼠具有明显的急件肝、肾毒性。

Objective： To observe the acutea hepatotoxicity and nephrotoxicity of geniposide on α-naphthylisothioeyanate （ANIT） -induced jaundice rats, and to provide scientific basis for the clinical application of gardenia. Method： One hundred and ninety rats were divided into three following groups： the normal group, the model group and the geniposide group. The alanine aminotransferase （ALT）, aspartie transaminase （AST）, alkaline phosphatase （ALP）, total bilirubin （TBIL）, blood urea nitrogen （BUN） and creatinine （CREA） activity in serum were detected at different time. The morphological changes of liver and kidney tissue were observed under light microscope. Result： Compared with the normal group, the levels of AST, ALP, ALT, TBIL, BUN and CREA increased in the model and geniposide groups. The results in the geniposide group were even worse fi）r AS＇F, ALP and ALT at 48, 72 h, for BUN and CREA at 24, 48, 72 h than the model group. Under light microscope, serious pathological damage in liver and kidney tissue of rats were observed in the model and geniposide groups, which were more serious at 48, 72 h. Conclusion： Geniposide could cause acute liver and kidney injury on jaundice rats.