OBJECTIVETo investigate the changes of NF-kappa B binding activity, the expression of PPARr and their correlation in the liver of rats with fatty liver disease (FLD) induced by different pathogenic factors and to investigate the molecular mechanism of the inflammation in FLD.

METHODS40 Wistar rats were randomly divided into 4 groups of ten each: normal group, alcohol group, fat-rich diet group, alcohol adding fat-rich diet group. The rats were sacrificed at the end of the 16th week from the starting day of the experiment. Serum and liver specimens were collected. Histological specimens were stained with HE, SudanIV, and Masson and then studied microscopically. The ultrastructural changes were also checked under an electron microscope. NF-kappa B binding activity and the expression of PPARr mRNA were determined by electrophoretic mobility shift assay (EMSA) and RT-PCR respectively. The correlations between NF-kappa B binding activity and the expression of PPARr and the biochemical indexes were analyzed.

RESULTSSteatosis, inflammation, necrosis and fibrosis were present in livers of the rats of all the experimental groups, and were most severe in the alcohol adding fat-rich diet group. NF-kappa B binding activity was markedly increased in the livers of the alcohol group (142+/-16.32) and of the alcohol adding fat-rich diet group (238+/-19.14) in comparison to the livers of the normal (73+/-9.24, F = 6.36, 17.93) and those of the fat-rich diet group (84+/-10.38, F = 5.96, 16.20). Binding activity was higher in the alcohol adding fat-rich diet group than that in the simple alcohol group, but there was no difference between those of the fat-rich diet and normal groups. The level of PPARr mRNA was lower in the livers of the alcohol, fat-rich diet, alcohol adding fat-rich diet groups (0.2530+/-0.069, 0.3647+/-0.082, 0.1226+/-0.054) than that of the controls (0.8097+/-0.094) (F = 15.43, 7.24, 21.45). NF-kappa B binding activity was correlated positively with the level of serum TNF alpha (r = 0.527, 0.639) and the content of MDA in the liver homogenates (r = 0.723, 0.537), but negatively with the expression of PPARr in the livers of the alcohol and the alcohol adding fat-rich diet groups (r = -0.568, -0.891).

CONCLUSIONThe enhanced nuclear factors NF-kappa B binding activity and decreased expression of PPARr play a pivotal role in the inflammatory response of FLD induced by alcohol and fat-rich diet. It may provide a new idea for treating FLD effectively.