The role of NF-κB,ICAM-1 and inflammatory cytokines in the liver injury of acute pancreatitis in rats

Objective To investigate the role of nuclear-KB(NF-κB),intercellular adhesion molecule-1(ICAM-1)and inflammatory cytokines in acute panereatitis(A.P)with liver injury in rats. Methods Thirty-six SD rats were randomly allocated into acute panereatitis group(AP group)and sham operation group(SO group).AP model was induced by retrograde injection of 3.5% sodium taurocholate into the pancreatic duct in rats.The histopathological changes of the pancreas were observed and studied by light microscopy at 3,6 and 12 h after operation.The pathological changs of liver were examined under light microscopy and electron microscopy.The serum levels of alanine aminotransferase(ALT)were deter- mined,the changes in blood levels of TNF-α,IL-1βand IL-6 were tested by radioimmunoassay(RIA) method,and the levels of serum IL-10 were measured by enzyme linked immunosorbent assay(ELISA)at different time points.The expression of TNF-αand IL-6 mRNA in the liver was detected by real time poly- merase chain reaction(RT-PCR).NF-κB and ICAM-1 activity in the liver was examined by immunohisto- chemical methods.Results Histopathologic examination revealed the occurrence of pancreatic inflamma- tion in AP group.Pathological changes appeared in liver of AP group.With the development of AP,the lev- els of serum ALT,TNF-α,IL-1β,IL-6 and IL-10 in AP group were increased significantly as compared with SO group(P0.05):the serum levels of TNF-αwere increased significantly at 3-6 h,and reached peak at 6 h;the serum levels of IL-6 were increased significantly at 3 h and then decreased sligntly.NF-κB activity was strengthened at 6 and 12 h,but there was no change in ICAM-1.There was significant differ- ence in the NF-κB expression among the three AP groups(x~2=15.048,P0.05).The expression of TNF-αand IL-6 mRNA in liver tissue of the AP group was also stronger than that in SO group in 3-12 h (P0.05),and the expression of TNF-αmRNA was increased at 3 h and reached the peak at 6 h.The expression of IL-6 mRNA reached the peak at 3 h and was only decreased sligntly after 3 h.Conclusion The activation of hepatic NF-κB is associated with the liver injury by regulating the expression of TNF-αand IL-6 mRNA in AP.ICAM-1 has no obvious effect on the liver injury in the early stage of AP.