The Production Of Oxygen-derived Free Radical And The Restraint Of Gliotoxin In Ischemia Reperfusion Injury In Liver

A period of blood-blocking is required for a number of surgical procedures onthe liver, especially when dealing with extensive hepatic trauma or resecting largeⅠintrahepatic lesions. The hepatic ischemia and hypoxia can cause hepatic cellularinjury. When restoring the blood supply, the liver is subjected to an aggravatingimpairment. This is termed Ischemia-Reperfusion Injury. The insult on the liver afterthe onset of ischemia-reperfusion injury is a result of the interplay between differentcomplex mechanisms. In these mechanisms, oxygen-derived free radicals (ODFR) arebelieved most important. At this background, the research of pharmaceuticals ofpreventive Ischemia-Reperfusion Injury developed step by step. Several studies haveshown that the administration of Vitamin C, Vitamin E, Coenzyme Q10(CoQ10) andSOD results in protected the organ from ischemia-reperfusion injury duringtransplantation and liver resection. Gliotoxin is one of the better members of theepipolythiodioxopiperazine (EPT) class of fungal metabolites and is produced by anumber of Penicillium and Aspergillus species and Candida. Gliotoxin has a varietyof toxic effects such as suppression of antigen processing, induction ofmacrophagocytic apoptosis and inhibition of transcription factor NF—κB activation.This study established model of hepatic Ischemia-Reperfusion Injury of SD rats, andwas designed to determine whether gliotoxin has the inhibitive effect on thesuperoxide anion in hepatic ischemia-reperfusion injury. At the same time,biochemical methods was used to detect Malondialdehyde (MDA), Xanthine oxidase(XOD), the common vigor of anti-superoxide anion of hepatic tissue in order to tryand find the localization of superoxide anion.Setup a model of hepatic Ischemia-Reperfusion Injury in rats. NinetySprague-Dawley rats were randomized into three groups: sham group (groupⅠ),ischemia-reperfusion group (groupⅡ), and group of Gliotoxin influenced(groupⅢ).The rats in sham group were only exposed the left-middle liver and haptic stem.The rats in Ischemia-Reperfusion Injury group were blocked the blood flow of left and middle liver, make them ischemia for thirty minutes, then re-circulate the bloodflow for forty-five minutes. The rats in groupⅢwere blocked the blood flow of leftand middle liver, make them ischemia for thirty minutes, then re-circulate the bloodflow for forty-five minutes. When fabricate the electron microscope specimen, add ingliotoxin. The left and middle liver of all three groups were taken out of andfabricated to microscope specimen. The Seguchi-koubayashi technique was used todetect the superoxide anion and biochemical techniques were used to detect theMalondialdehyde (MDA), Xanthine oxidase (XOD), the common vigor of anti-superoxide anion of hepatic tissue.Data are expressed as means±S.E.M. Comparisons between'groups were madeby the Student's t test, an associated probability of p＜0.05 was considered to besignificant.The observation results of electron microscope show the specimens of controlhave no deposition of dense particles. While the specimens of Ischemia-ReperfusionInjury group have many deposition of dense particles. And the specimens of the thirdgroup.have little deposition of dense particles. The level malondialdehyde (MDA),xanthine oxidase (XOD) and the common vigor of anti-superoxide anion of hepatictissue of Ischemia-Reperfusion Injury group increase significantly.The model that blocked the blood flow of left and middle liver, make themischemia for thirty minutes, then re-circulate the blood flow for forty-five minutes is asimple and useful model; Gliotoxin has significant protective effects against hepaticIschemia-Reperfusion injury; The level malondialdehyde (MDA), xanthine oxidase(XOD) and the common vigor of anti-superoxide anion of hepatic tissue ofIschemia-Reperfusion Injury group increase more significantly than beforeIschemia-Reperfusion Injury.In the finality, the problems requiring further studies are discussed.