The Protective Effect Of MG132 On The Liver After Ischemia Reperfusion Injury By The Activity Of NF-kB In Rats

Hepatic injury secondary to ischemia and reperfusion is an important clinical issue,it often happens during the reconnection after circulation broken such as liver transplantation, liver resectional surgery,provoke failure of hepatic function and MODS with upper morbidity and mortality.The data shows that the rate of success is obviously increasing on liver transplantation,now 1-year survival rate have reached 85%,5-year survival rate is 70%,survival rate after the re-transplantation is 50%.But the morbidity of hepatic primary graft nonfunction is still 2%-23%, the important reason that cause primary graft nonfunction is hepatic ischemia reperfusion injury, except the quality of donor, the technology of operation,immunoreaction in the perioperative period.The study confirm that ATP is decreasing, glycolysis is aggravated, mitochondrial is edema and cracking,balance of ion inside cells is turbulenced,through activate the rely on Ca2+ protease and damaging the tissue when hepatic ischemia happen.After the reperfusion,the endothelium cell is damaged, kupffer cell is activated,various mediators of inflammation chemotaxis and get together the neutrophil which cause liver to release the protease and free radical to aggravate the damage of tissue.And NF—kB can transcripte and adjust the gene of various mediators of inflammation during the reperfusion.When NF—kB is activated , IkB degradation need be restrained.Proteasome inhibitor decrease the degradation of IkB in the proteasome through restraining the way of ubiquitin-proteasome.The study is to investigate the role of proteasome inhibitor MG132 on NF-kB acivity in rats after hepatic ischemia reperfusion injury.We adopt lobar hepatic ischemia reperfusion injury model of rat, randomly divided thirty two healthy Wistar rats into 4 groups. They are normal control group, subjected to 90 minutes lobar hepatic ischemia group, underwent 90 minutes hepatic ischemia followed by 120 minutes reperfusion group, after hepatic ischemia reperfusion with proteasome inhibitor MG132(Z-Leu-Leu-Leu-al) (30mg/Kg) treatment group.In addition to histological examination of the liver, plasma alnine aminotransferase (ALT) , aspartate aminotransferase (AST)levels were respectively measured in each group. The activity of NF-kB was determined by sABC immunohistochemistry. The activity of myeioperoxidase(MPO) in liver tissue was also determined.Work Results are histological damage occurred in 90 minutes hepatic ischemia and 90 minutes hepatic ischemia followed by 120 minutes reperfusion(I/R) and I/R with MG132 treatment group. It was characterized by hepatic arrangement turbulence, hepatic lobules distortion, congestion in liver sinusoids, hepatocyte swelling or necrosis, and neutrophils infiltration. These changes were markedly alleviated in I/R with MG132 treatment group (p﹤0.01), compared to I/R group. Almost normal control group didn't have activity of NF-kB. But the activity of NF-kB was markedly increase in I/R group (p﹤0.01). Plasma ALT and AST levers were significantly increased in I/R group, while they were much lower in I/R with MG132 treatment group (p﹤0.01) . In addition , liver tissue MPO activity was significantly elevated in I/R group, while it...