Study on the Role of COX-2、TLR4/HO-1 in Ischemia Reperfusion Injury of Whole/partial Liver Transplantation in Rats
|Keywords||COX-2 (Cyclooxygenase-2) TLR4 (Toll-Like Receptor 4) HO-1 (Heme Oxygenase-1) Ischemia-reperfusion injury (IRI) Whole liver / liver transplantation Rats|
Objective To investigate the COX-2, TLR4, HO-1 in rat liver / partial liver transplant ischemia-reperfusion injury (IRI) expression, meaning its mechanism of action, for in-depth study of COX-2, TLR4, HO-1 The specific mechanism of action, clinical prevention and treatment of liver transplantation IRI in liver transplantation IRI provides a new theoretical foundation. Methods Male Wistar rats were randomly divided into four groups: normal control group (O); liver transplantation group (LT); 50% partial liver transplantation group (PLT); NS398 intervention group (NS). Successful rat liver / liver transplantation model, respectively graft ischemia - 3,6,12,24 h after reperfusion, recipient rats were sacrificed, semi-quantitative reverse transcription - polymerase chain reaction (RT-PCR) detection COX-2, TLR4, HO-1 mRNA expression; Immunohistochemistry showed that COX-2-positive cell distribution rule; enzyme-linked immunosorbent assay (ELISA) detection level of serum TNF-a and IL-10; ALT / AST changes in expression levels The combination of light and electron microscopy to determine the degree of tissue damage. At each time point within the 50% partial liver transplantation group (PLT) COX-2 mRNA expression levels were higher than the liver transplant group (LT), its group at each time point ALT / AST expression and histopathological damage, injury TNF -a protective IL-10 levels than those of the whole liver transplantation (LT).; NS398 inhibition of COX-2 expression in the intervention group (NS), the same group compared to whole liver transplantation (LT) ALT / The histopathological damage increased AST elevated expression of TNF-a and IL-10 expression levels increased (P <0.05). The expression of COX-2 in liver transplant ischemia reperfusion injury mechanisms necessary to inhibit the expression can aggravate graft ischemia-reperfusion injury. NS398 COX-2 inhibition did not affect the expression of TLR4 the relatively high PLT group endotoxemia (LPS), TLR4 sensitive. HO-1 as an endogenous protective factor for liver transplantation IRI necessary NS398 significantly reversed the high glucose inhibits the expression of HO-1. Conclusion COX-2, TLR4, HO-1 expression for liver transplant ischemia reperfusion injury mechanisms are necessary. COX-2 involved in liver transplantation IRI, the liver IRI important effector molecules, one of the participants of the IRI; may play a protective role reduce the transplanted liver ischemia-reperfusion injury. TLR4 and COX-2 no significant correlation. HO-1 may be a downstream product of the COX-2. The results of this study, COX-2 is included in a complex injury regulation important effects of substances, the result of its role in the network may rely on its downstream prostaglandin product in promoting injury - anti-proportional relationship between the injury and the specific regulation and mechanism of action pending further study.