LPS increases the liver injury via TLR4-dependent manner in mice with acute obstructive jaundice

Objective To investigate whether LPS increase the liver injury and involved mechanism in mice with obstructive jaundice.Methods 42 of C57BL/10J(WT)male mice were randomly divided into NS group(n=21)and LPS1 group(n=21),and LPS2 group as C57BL/10ScnJ(TLR4-/-)male mice(n=21).All mice were subjected to common bile duct ligation(CBDL),then the LPS1 and LPS2 groups were injected with LPS(8 ng/μL,10 ng/g body weight)via common bile duct after CBDL operation;the NS group was injected with equal amount of saline.The blood samples and liver tissues were collected at 6,12,24 h(n=7)after treatment and prepared for further analysis.The concentrations of serum ALT 、TBIL、DBIL were measured by automatic biochemistry analyzer;the levels of serum TNF-α and IL-6 were measured by enzyme-linked immunosorbent assay;the expressions of TLR-4 mRNA in the liver tissue were detected by RT-PCR;histological analysis showed the injury of the liver tissue and the distribution of NF-κB were detected by immunohistochemical staining.Results Liver tissue injury was more severe in the LPS1 group compared with the NS and LPS2 groups.mRNA level of TLR-4 in liver tissues was increased 6 hours after CBDL and LPS injection in LPS1 group,and peaked at 24 hours;No detection of TLR4 mRNA in LPS2 group;TNF-α and IL-6 secretions were significantly increased (P0.01)in LPS1 group;NF-κB was obviously expressed in the nucleus of hepatic cells in the LPS1 group at 24 hours after surgery,and slightly expressed in the NS group and LPS2 group.Conclusion LPS increased the liver injury after mice were subjected to CBDL.The activation of NF-κB and release of TNF-α and IL-6 were correlated with the higher expression of TLR4 in the liver and might be involved in this process.