Role Of Cyclooxygenase-2 And PGI₂/TxA₂ On Ischemia-reperfusion Injury In Liver Transplantation In Rat

Objective:Study the role of cyclooxygenase-2(Cox-2)and PGI₂/TXA₂ on ischemia-reperfusion injury after liver transplantation in rat,and to investigate possible mechanisms.Method:Rats were randomly divided into three groups:control group(E1),liver IR group(E2),NIM and liver IR group(E3),orthotropic liver transplantation group(E4),NIM and orthotropic liver transplantation group(E5).Cold preservation group(E6);To obtain the samples 3h,6h,12h,24h post operation or portal vein opened and obtain the samples 1h/3h after cold preservation;Alanine aminotransferase(ALT)and Aspartate aminotransferase(AST)was measured; Radio-immunity assay was used to detect 6-Keto-PGF-1a,TXB2(stable metabolites of the TXA2 and PGI2)in tissue and plasma in every group;Two step-RT-PCR and Immunohistochemistry were used to detect the expressions of Cox-2 and location; Hematoxylin Eosin staining was used to classify the injury extent of every samples, Enzyme linked immunosorbent assay ELISA was used to detect the value of TNF-a in E6 group.Result:1.The expressions of Cox-2 and the value of 6-Keto-PGF-1a,TXB2 in E2,E3,E4, E5,E6 group were significantly higher than in the E1 group(P＜0.05), especially the TXB2,ratio of TXB2 / 6-Keto-PGF-1a was increment in E2 E4 and E6;The dates of the E3 and E5 were significantly lower than the E2 and E4 group(P＜0.05),TXB2 was reduced obviously,and the ratio of TXB2/ 6-Keto-PGF-1a was diminution;2.Immunohistochemistry examination showed that injury of liver injury was significantly lightened in E3 and E5 group compared with the E2 and E4 group; Cox-2 was degraded in Cox-2 inhibitor preconditioning both in E3 and E5 groups. 3.In E6 group,the TXB2 / 6-Keto-PGF-1a and TNF-a were significantly higher than E1 group after 1h/3h cold preservation.But our dates did not have statistical significance between 1h and 3h.4.The level ofAST,ALT in blood serum,the date of E2,E3,E4,E5 was significant hingh compared with E1(P＜0.05)E2 and E4 was significant hingh compared with E3 and E5 groups,E4 group was significant hingher than E2 group(P＜0.05);Conclusion:Our dates showed that Cox-2 has harmful effects in I/R injury in liver-transplantation and Cox-2 inhibitor may protect the liver.The mechanism was partly reduction of TXB2 and regulating balance of TXA2/PGI2.TXA2/PGI2 and TNF-a may have important effects in liver cold preservation injurys.