OBJECTIVEThe expression of hepatic lipopolysaccharide (LPS) receptors in a rat nonalcoholic steatohepatitis (NASH) model was studied in order to explore the pathogenesis of NASH.

METHODSForty-five male SD rats were fed with a high fat diet. These rats were sacrificed after high fat feeding at 8, 12, 16, 24 weeks. Hepatic expressions of CD14 were observed by immunohistochemistry and expressions of TLR4 were detected by RT-PCR. Hepatic expressions and serum levels of TNFa were measured by RT-PCR and ELISA. Some rats fed with normal rat food served as controls.

RESULTSAt the 8th week fatty livers appeared, and hepatic expressions of CD14 (25.9+/-1.9) and TLR4mRNA (1.75+/-0.81) were upregulated compared to those in the control group (25.9+/-1.9 vs 12.4+/-0.7, 1.75+/-0.81 vs 0.98+/-0.33, P < 0.01, t > 2.756 and P < 0.05, t > 2.045). The hepatic expressions of the two kinds of receptors increased with the appearance of NASH at week 12 (61.8+/-1.9 and 1.88+/-0.72, P < 0.01, t > 2.756 and P < 0.05, t > 2.045), They reached to their peaks at week 16 (71.5+/-1.3 and 5.64+/-0.87, both P < 0.01 and t > 2.756), and decreased slightly at week 24 (67.7+/-6.6 and 4.98+/-0.72, both P < 0.01 and t > 2.756). Hepatic expressions and serum levels of TNFa also increased starting at week 8, and remained at that high level from week 8 to week 24.

CONCLUSIONThe hepatic expressions of CD14 and TLR4 were up-regulated gradually in the established rat NASH model. It may be one of the factors responsible for the increase of hepatic sensitivity to LPS injury of the NASH rats and may play an important role in the pathogenesis of NASH.