Abstract: Objective To observe the influence of 4-week mimic metabolic endotoxemia on hepatic histology and Toll-like receptor 4（TLR4） signaling pathway in mice. Methods Thirty male C57BL/6J mice were randomly divided into normal （n=10） and endotoxin（n=10） groups,fed with normal diet,and high-fat（n=10） group,fed with high-fat diet. The mice in endotoxin group were implanted with subcutaneous osmotic minipump to infuse endotoxin at 300 μg·kg^-1·d^-1 for 4 weeks. The mice in normal group were implanted with minipump filled with saline as control. At the end of the 4th week,the serum endotoxin level were detected. NAFLD activity score（NAS） of liver tissue was evaluated. The mRNA levels of hepatic TLR4,MyD88 and TRAM were detected by real time PCR. Results Serum endotoxin level in endotoxin group[（0.62±0.04） EU/ml] was significantly higher than that in normal group [（0.50±0.06） EU/ml,P<0.05] and in high-fat group [（0.49±0.05） EU/ml,P<0.05]; The dominant histology change of liver in endotoxin mice was simple steatosis and the NAS score was（2.30±0.49）,while the mice in high-fat group had more severe hepatic inflammation and the NAS score was（4.20±1.61）,which was significantly higher than that in the endotoxin group（P<0.05）;The TLR4 mRNA level in endotoxin group was 5.12 times higher（P<0.01） and TRAM mRNA level was 3.46 times higher（P<0.01） as compared with in normal group, but the MyD88 mRNA levels in the three groups had no significant difference. Conclusion Four-week mimic metabolic endotoxemia induces hepatic steatosis with increased levels of hepatic TLR4 and TRAM mRNA,but has no effect on the hepatic MyD88 mRNA.

Key words: Nonalcoholic fatty liver disease, Metabolic endotoxemia, High-fat diet, Toll-like receptor 4, Mice