Application of PPARαtransgenic mice in the evaluation of drug toxicity
10.3969/j.issn.1005-4847.2015.03.018
- VernacularTitle:PPARα转基因小鼠在药物毒性评价中的应用
- Author:
Yinli HE
;
Xun GUO
;
Xianli ZHAO
;
Yanyu PEI
;
Jingjiang SUN
;
Hong GAO
- Publication Type:Journal Article
- Keywords:
PPARαtransgenic mouse;
PPARαagonist;
Hepatotoxicity;
Nephrotoxicity
- From:
Acta Laboratorium Animalis Scientia Sinica
2015;(3):316-320
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore whether PPARαtransgenic mice are more sensitive animal models in the evalua-tion of toxicity of PPARαagonists.Methods Twenty-eight 8-week old PPARαtransgenic 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, kid-neyweretestedafterthedrugadministration.Thegrowthofmicewasalsorecorded.Results ①Bloodbiochemistry:Com-pared 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, PPARαtransgenic mice are more sensitive in evaluation of hepatotoxicity and nephrotoxicity of PPARαagonists .It is a new animal model .
