The Protective Effects And Mechanisms Of Nitric Oxide During The Liver Ischemia-reperfusion Injury In Rats

AIM: Prolonged hepatic ischemia followed by reperfusion results in severe injury that contributes to the morbidity and mortality of shock, transplantation, and liver surgery. Nitric oxide(NO),as a potent vasodilator, has reported to be important for the liver hR injury. But it has recently been recongnized that NO has various effects on hepatic hR injury depending on different mechanisms. In this study, we investigated the role of NO, and evaluated the effect of the NO donor, L-arginine, on prolonged warm hR injury in the rat liver. METHIEODS: Ninety male SD rats were divided into three groups: sham operation (Group I) and 70 mm ischemia followed by reperfusion with being given L-arginine(100 mg/kg) intravenously just before the re-flow (Groupffl) or given saline (Group 4 II ).Rats were sacrificed at 0,1,3,6 and 12 hr after reperfusion.Serum alanine aminotransferase(ALT), methylenedi-oxyamphetamine (MDA) ,reduced gluta- thione (GSII), glutathione peroxidase(GSH-PT), glutathione sulfurtrans- ferase(GSH-ST) and plasm tumor necrosis factor- a (TNF- a) were investigated. Liver sections were evaluated at the end of ischemia and at 1,3,6,12 hr after reperfusion. Apoptosis at 6 hr after reperfusion was determined by in situ staining for apoptotic cells using TdT-Mediated dUTP-digoxigenin neck-end labeling (TUNEL),and morphology on electron microscopy. The expression of Bcl-2 was stained with an anti-Bcl-2 monoclonal antibody and visualized with SABC method. RESULTS:Serum AST, MDA, GST-PX and GSH-ST elevated significantly in Group II .Serum GSH decreased significantly from 3 hr after reperfusion. Plasm TNF- a increased significantly after reperfusion in Group II .The NO donor,L-arginine could reverse these changes significantly (P<0.05).The elevation of serum ALT,MDA,and plasm TNF- a was suppressed in the L-arg-treated group.In situ staining of liver biopsy specimens using TUNEL showed significant apoptosis at 6 hr after reperfusion in Group II .A decrease in TUNEL-positive cells was noted in Group ITI(P<0.05).The numbers of Bcl-2-positive cells have no significant differences in the three groups. CONCLUSION: These results indicate that L-arginine can reverse the changes of serum GSH, GSH-PX and GSH-ST, and inhibited the increase of plasm TNF- a in the hepatic hR injury. And it can inhibit apoptosis of hepatocytes. They may correlate with the protection of L-arginine in the hepatic hR injury.