Experimental Studies On The Protective Effect Of Edaravone Against Hepatic Ischemia-reperfusion Injury In Rat

Objective: Hepatic ischemia reperfusion injury is a key and common phenomenon in the procedure of liver transplantation, liver partial excision, hemorrhagic shock, cardiogenic shock, etc and in some clinic disease. After reperfusion, generous active oxygen was created and bulk of mediators of inflammation such as nuclear factor-κB , tumour necrosis factor-α, interleukin-1 intercellular cell adhesion molecular-1, P and L-selectin etc were releasing in the activation of macrophage, lymphocyte and neutrophilic granulocyte, to succeed in inflammatory reaction and cell death. If some measurement of preconditioning was done before hepatic ischemia reperfusion, such as heat stress, ischemia preconditioning and injection of drug etc to elevate tolerance of organism to stress of hepatic ischemia reperfusion, liver histiocyte injury was extenuated and hepatic function was restored quickly. Edaravone is a neotype free radical scavenger, and no side effect was acquired in a great quantity of research.. Therefore, to investigate the protective effect of edaravone against hepatic ischemia-reperfusion injury in rat and clarify its possible mechanism, there was a considerable significance in guiding clinical performance of liver surgery and liver transplantation such as administration in procedure of liver transplantation, therapy after liver partial excision, prophylactic administration before block the first porta hepatis in the operation.Methods: The model of 70% hepatic ischemia-reperfusion was established in SD male rat. Twenty four healthy rats were randomly divided into 3 groups, S: sham operation group (n=8): Just open the abdominal cavity and mutilate peripheral ligaments of the rat liver, then to dissect and not block the first porta hepatis, eventually, close the belly cavity. IR: ischemia-reperfusion group (n=8): open the abdominal cavity along the median line on the epigastric zone, and dissect the first porta hepatic to find the porta hepatis that affluxes to the left and middle liver lobe in SD rat, then block it with a bulldog clamp that result in no injury to tissue, and the model of 70% hepatic ischemia-reperfusion was established. The bulldog clamp was unclamp after 1h of ischemia, and the ischemia liver lobe was reperfused.ED: edaravone treatment group (n=8): administrate 10mg/kg of edaravone via vena dorsalis penis before blockade, the other operation was same as that of IR group.After 2h of reperfusion, Blood was drawed in the inferior vena cava of rat to examine the enzyme levels in serum including ALT and AST. The SOD,MDA,MPO in liver tissues were measured. The expression of NF-κB in liver cell was determined in Western-blot and histologic changes was observed in HE staining. The orientation of NF-κB in the liver cell was detected in immunohistochemistry and its expression was also calculated.Results: After 2 hours of ischemia-reperfusion, the levels of ALT,AST,MDA and the activity of MPO and NF-κB expression was significantly higher than that in S group, and meanwhile the protein of NF-κB was activated and transferred into the liver cell nucleus ,IR group more obviously, the injury of liver tissue in IR group was more obviously, but the activity of SOD was decreased. After treatment of edaravone, the abnormal of all above parameters were diminished remarkably(P <0.01).Conclusions: This study suggests that edaravone has a protective effect on liver against ischemia-reperfusion injury in rat. The mechanism of protection may be related to its radical scavenging, inhibiting of lipid peroxidation, and its suppressing of NF-κB activation.Therefore we presume that there is feasibility about its application on the clinical performance of liver surgery, but further authentication is required about whether there is analogical effect in the human body.