Study on an animal model of nonalcoholic steatohepatitis induced by high-fat emulsion combined with liver injury drugs
OBJECTIVE To establish an animal model of compound nonalcoholic steatohepatitis(NASH),to further reveal the pathogenesis of NASH and to provide an ideal tool for evaluating the efficacy of new drugs for prevent and treat NASH.METHODS Three factor two level orthogonal design was used.After 5 days of dexamethasone,tetracycline,high-fat emulsion and combination of dexamethasone and tetracycline administration,serum liver function,blood lipid and other biochemical indexes,liver lipid level were measured,and liver histopathology was analyzed.RESULTS Dexamethasone and tetracycline alone could cause significant abnormalities in liver function level,blood lipid level and liver lipid level,while high-fat emulsion alone had little effect on liver function.The results of factorial analysis showed that dexamethasone was the key factor causing the abnormality of multiple indicators,including ALT,AST,TBiL,DBiL,blood lipid and liver lipid.Tetracycline only affects some indexes,including transaminase and bilirubin.High fat emulsion mainly affected the cholesterol level in serum and liver.The combination of dexamethasone and high fat emulsion had obvious synergistic effect on increasing serum and liver TC levels.The main factor causing the increase of liver TG was dexamethasone.When combined with tetracycline and HF,it could produce a significant synergistic effect.CONCLUSION Both dexamethasone and liver injury drugs or high-fat emulsion have significant synergistic effect,suggesting that the formation of NASH is related to endocrine,liver function and blood lipid level.The combination of dexamethasone and high-fat emulsion can form a relatively ideal NASH mouse model in a relatively short time,which is a relatively simple and good animal model for screening drugs to prevent and control NASH.
Orthogonal designNonalcoholic steatohepatitisDexamethasoneTetracyclineHigh fat emulsionAnimal model
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