Effect And Mechanism Of Glutathione On The Rat Liver Ischemia Reperfusion Injury

In the liver surgery ,massive hemorrhage is clearly a major factor that cause liver failure and death after operation,so we often need to occlude the vascular inflow to the liver.But the use of this technique has been limited because that the function and structure of liver is damnified during the ischemia period,moreover this will deteriorate in reperfusion period,and this was called the ischemia reperfusion injury(I/R injury).The liver injury induced by ischemia reperfusion is an important and common clinical problem and may lead to postoperative liver failure and death,so it is necessary to study it's mechanism.The mechanism of the liver ischemia reperfusion injury is complexAccording to the recent research,it is general believed that the recruitment of the leukocyte,especially the neutrophilic leukocyte,into hepatic microvascular,play a critical role in the ischemia reperfusion injury,and it may lead to the liver failure and even the multiple organs dysfunction syndrome.Now,there are more and more studies on the adhesion molecules(AM) in the liver ischemia reperfusion injury.From the discover and futher study of the adhesion molecule,the mechanisms of the recruitment and activation of the neutrophilic leukocyte into hepatic microvascular have become clear gradually. P--selectin,as one member of the adhesion molecule families,mediates the interactions between activated neutrophilic leukocyte and endothelial cells,and play an important role in the liver ischemia reperfusion injury. P-selectin is stored in granules called Weibel - Palade bodies of endothelial cell and a -granules of platelet,which is mobilized within minutes to the surface when cultured endothelial cell are exposed tohistamine,thrombin,or oxidants et al.There are many drugs which have been observed the changes of P-selectin expression in the hepatic tissue after the liver ischemia reperfusion.But the effect of glutathione(GSH) on it have not experimental testimony in our country.The study was conducted to investigate the effect of Glutathione which was injected from the stem of portal vein before hepatic ischemia on the rat liver ischemia reperfusion injury and clarify its possible mechanism.Materials and Methods36 male Wistar rats were randomized into 3 groups:(1)sham operation group(group SO),(2)ischemia reperfusion group(group I/R),(3)glutathione preconditioning group(group GPC).In the model of rat liver ischemia reperfusion,all structures in the portal triad(hepatic artery,portal vein and bile duct) to the left and median liver lobes were clapped for 45 minutes.In the I/R group, 0.9%NS (3ml/kg ) was injected from the stem of portal vein 15 mintures before the hepatic ischemia;in the GPC group, 200mg/ml GSH (3ml/kg) was injected from the stem of portal vein 15 mintures before the hepatic ischemia. After one hour of reperfusion the following parameters were measured:ALT(alanine aminotransferase) and AST(aspartate aminotransferase) level in serum, MDA (malondialdehyde) content, GSH content,myeloperoxidase(MPO) activity and expression of P-selectin in left liver lobes.The serum levels of ALT and AST were detected with biochemical analyzer;the expression of P-selectin in the ischemic liver tissue were assayed by immunohistochemistry,the pathological change of liver observed under microsope.All data were analyzed with SPSS 10.0,P valus less than 0.05 were considered significant.Results1. In the group I/R and group GPC,after the forty five minutes ischemia and one hour reperfusion, the serum levels of ALT , AST and the content of MDA, MPO activity in the left liver lobe were obviously higher than those in group SO(P<0.05) . the serum levels of ALT , AST and the content of MDA, MPO activity in the left liver lobe in group GPC is significant lower than those in group I/R(P<0.05) .2. In the group I/R and group GPQafter one hour reperfusion,the GSH content in theleft liver lobe were obviously lower than those in group SO(P<0.05). the GSH content in group GPC is significant higher than those in group I/R(P<0.05) .3. After one hour reperfusion, under microscopic examination the structure of the left liver lobe was unsharpness,and the adema ,necrosis of hepatic cell , infiltration of inflammatory cells in the hepatic tissue could were obvious in the I/R group;But the changes were milder in the GPC group's.4. In the group I/R, after one hour reperfusion,the expression of P-selectin on the surface of the live cells, endothelial cells is significant higher than the group SO's(P< 0.05). The expression of P-selectin in group GPC is significant lower than group I/R's(P<0.05).Conclusion1.Injection of GSH from portal vein before liver ischemia may significiently increase the content of GSH in heptatic tissue which has underwent I/R injury.2. Precondition of GSH from portal vein can not eliminate the liver damage induced by the I/R injury completely,which indicates that there may be other factors involed in the liver I/R injury.And the mechanisms need to be studied further.3. Precondition of GSH from portal vein can reduce the liver damage induced by I/R injury. Two majory reasons are:(1)it might protect hepatic cells from damage of free radical;(2)it might inhibit P-selectin expression in liver which reduces the leukocyte adhesion and infiltration during I/R injury.