Abstract: Objective To describe the kinesis changes of TLR4 mRNAexpression,serum TNF-α and heaptocyte apoptosis in lipopolysaccharide(LPS)-induced acute liver failure.Methods Acute liver failure was established by intraperitoneal injections of D-galactosamine(400 mg/kg)and lipopolysaccharide(100 ug/kg)in female Wistar rats.Mortality and survival time were recorded in₁₀ rats.Ten rats were sacrificed at 4,8,and 12 hours after treatment.Liver function test,serum TNF-α levels,IL-10 were measured,as well liver pathology studied.The apoptosis of liver cells was detected by TUNELassay.Results 80% rats died from acute liver failure after administration of D-galactosamine/lipopolysaccharide,with mean survival time of(15.6±1.8)hours.Liver function tests were compatible with liver massive necrosis.Plasma level of TNF-α and liver cells apoptosis increased,The expression of TLR4 mRNAincreased at every time points in liver tissue,which was positively correlation with concentration of plasma TNF-α(r=0.709,P=0.000)and no correlation with IL-10.Conclusion The results showed that TLR4 were involved in inducing the generous production of TNF-α,which activating inflammatory cascade reaction and initiating liver cell apoptosis.It suggested that TLR4 would be the novel strategy to prevent the development of lipopolysaccharide-induced acute liver failure.

Key words: rat, acute liver failure, lipopolysaccharide, D-galactosamine, TLR4