Experimental study on the pathogenesis of nonalcoholic steatohepatitis / 中华消化杂志

ABSTRACT

Objective To study the pathogenesis of nonalcoholic steatohepatitis(NASH) in rat model. Methods Male SD rats were fed with a high fat diet for 12 weeks. Non alcoholic ateatohepatitis serum lipid, aminotransferase values and free fatty acid (FFA) levels were tested, the malondialdehyde (MDA) and superoxide dismutase (SOD) activity of hepatic tissue were also detected. Hepatic cytochrome P450ⅡE 1 (CYPⅡE 1) were detected in liver section by immunohistochemistry using CYPⅡE 1 specific antibodies and also with an immunohistochemical procedure for detecting the number of Kupffer cells. Results FFA concentrations of the serum and hepatic tissue were markedly increased, which was accompanied by an increase of MDA in hepatic tissue, whereas SOD activity of hepatic tissue was decreased. CYPⅡE 1 immunostaining was markedly increased, especially in the perivenous region. The number of Kupffer cells in NASH was significantly increased compared with control livers. Correlation analysis revealed that the increases in the levels of FFA correlated positively with the hepatic CYPⅡE 1 expression, the lipid peroxidation, and the pathological scores in the liver of NASH rats. Conclusion The increased FFA, highly expressed CYPⅡE 1, activated kupffer cells and increased lipid oxidate were all contributed to NASH.