| Objective To investigate the expression and role of COX-2,TLR4,HO-1 in ischemia reperfusion injury of liver transplantation of rats, which will be helpful for studying deeply mechanism of COX-2,TLR4,HO-1 in IRI and giving new view to prevention and treatment on IRI of liver transplantation. Methods Male Wistar rats were divided to 4 groups at random: normal group(O), liver transplantation group(LT), 50% partial liver transplantation group(PLT) and NS398 administrated group(NS). Whole/partial liver transplantation models of rats were built up successfully, and experimental animals were sacrificed after grafts ischemia-reperfusion 3, 6,12 and 24 hours. The expression of COX-2,TLR4,HO-1 mRNA and COX-2 protein were detected by RT-PCR and immunohistochemistry respectively. And the level of TNF-a and IL-10 were detected by ELISA after operation. The damage of grafts was judged by the level of ALT/AST and observed through light and electron microscope. Results The amount of COX-2 mRNA in different time after reperfusion in 50% partial liver transplantation group was all higher than whole liver transplantation group. And expression of ALT/AST and histopathologic damage, level of harmful TNF-a and protective IL-10 all higher than LT group too. Whereas, even if the expression of COX-2 was inhibited by NS398 in intervention group(NS), there were still higher ALT/AST and the more severe histopathologic damage, and the higher level of TNF-a and IL-10 than LT group(P<0.05). The expression of COX-2 is necessary to ischemia reperfusion injury after liver transplantation, but the inhibition to COX-2 also may increase ischemia reperfusion injury after liver transplantation. The inhibition of NS398 to COX-2 had no influence with TLR4. TLR4 was sensitive to high endotoximia(LPS) in group PLT. HO-1 is a protective endogenous factor, which includes in mechanism of IRI in liver transplantation. And NS398 can decrease expression of HO-1. Conclusion The expression of COX-2,TLR4,HO-1 is necessary to ischemia reperfusion injury after liver transplantation. COX-2 takes part in the ischemia reperfusion injury of liver transplantation and plays an important role in IRI of graft and is one of participator in IRI. There was a high level expression of COX-2 in partial liver transplantation group, but the inhibition to COX-2 also increased ischemia reperfusion injury after liver transplantation. So, it may be a protective role in liver transplantation to reduce IRI. TLR4 has no obviously correlation with COX-2, and HO-1 may be a product downstream of COX-2. This study showed, COX-2 was an important effective factor contained in a complex network after damage, and its effect maybe depends on the relationship between aggravate-anti damage of prostaglandins products downstream, the details of mechanism on accommodation and effect are worth to do a deeper study and research.
|
PDF Full Text Request