Basic mechanism study on lipopolysaccharide-induced murine liver injury

Objective: To observe signaling for LPS transduction ,mechanism of LPS-induced liver injury and LPS-induced hepatocyte apoptosis.Methods:LPS-induced endotoxin mouse was sacrificed at 3 hours,6 hours,12 hours,24 hours and 30 hours respectively. The liver tissue was stained with hematoxylun and eosin for histopathologic analyses. Hepatocyte apoptosis ,hepatic bax,bcl-2,Fas,Fasl were detected by use of immunohistochemistry technology.The expression of TLR4 were detected by use of semi-quantitative RT-PCR.Results:A large number of cells infiltrated portal areas with additional focal hepatocellular necrosis 24 hours after i.p. LPS. Hepatic TLR4 expression was significantly depressed from 6 to 12 hours after i.p. LPS,but recover at 24 hours. Hepatocyte apoptosis increased significantly at 3~6 hours after i.p. LPS,while returned to normal at 12 hours. At the same time,the expression peak of bax and Fas were at 3 hours after i.p.LPS,while the expression peak of bcl-2 and Fasl at 12 hours after i.p. LPS.Conclusion:1,LPS-induced liver injury was time-dependent. Hepatocyte apoptosis play a important role in its cell death. 2,The expression of TLR4 was time-dependent.The depression of TLR4 may be the protection of cells to LPS tolerance.3,Many kinds of factors result in LPS-induced hepatocyte apoptosis.