Application of PPARα transgenic mice in the evaluation of drug toxicity
Received:January 06, 2015  
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KeyWord:PPARα transgenic mouse;PPARα agonist;Hepatotoxicity;Nephrotoxicity
贺银丽 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
郭珣 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
赵显莉 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
裴彦宇 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
孙井江 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
高虹 中国医学科学院医学实验动物研究所, 北京协和医学院比较医学中心, 北京
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      Objective To explore whether PPARα transgenic mice are more sensitive animal models in the evaluation of toxicity of PPARα agonists. Methods Twenty-eight 8-week old PPARα transgenic mice (Tg) and 28 C57BL/6J mice (WT) with half males and half females were randomly divided into high dose group (400 mg/kg of clofibrate), low dose group (30 mg/kg of clofibrate) and solvent control group (10% sodium carboxymethyl cellulose). The time of gavage administration lasted 28 days. The blood biochemistry, organ coefficient and pathological changes of the heart, liver, kidney were tested after the drug administration.The growth of mice was also recorded.Results ①Blood biochemistry: Compared with the WT male administration group, in the Tg male administration group, the levels of blood creatinine (CREA) and aspartate aminotransferase (AST) were markedly increased (P<0.01, P<0.05). ② Organ coefficient: Compared with the Tg control group, the kidney coefficients of Tg administration group were significantly increased(P<0.01,P<0.05). ③Histopathology:Compared with the WT administration group, the pathological damages of liver and kidney were more serious in the Tg administration group. Conclusions Compared with C57BL/6J mouse, PPARα transgenic mice are more sensitive in evaluation of hepatotoxicity and nephrotoxicity of PPARα agonists.It is a new animal model.
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