Protective Effects Of Edaravone Precondition On Liver Injury And Kidney Injury Induced By Hepatic Ischemia-reperfusion In Rats

Objective: In order to observe the protective effects of edaravone preconditioning on liver injury and kidney injury induced by hepatic ischemia-reperfusion (I/R) in rats;To observe and analyze the feasibility of the protective effect of edaravone on liver injury and kidney injury by hepatic ischemia-reperfusion injury; These finding will provide a basis for clinical application.Methods: Thirty healthy male wistar rats weighing 250～300g, were randomly divided into 3 groups (n=10/group) :Sham operation group (group S), we just needed to anaesthetize these rats and open abdominal cavity to turn up the livers in order to expose hepatic aorta without blocking hepatofugal portal flow; Ischemia-reperfusion group (group I/R), we blocked hepatofugal portal flow for 30 minutes and unblocked for 4 hours; Edaravone group (group ED). Edaravone was administered 10mg/kg ( IP) 10 minutes before ischemia in Group ED. The contents of TNF-αin liver and kidney tissue bomogenate,meanwhile the SOD,MPO,MDA and serum ALT,AST in kidney and liver were determined. Results:1. The results of hepatic function:The levels of ALT and AST in liver serum bomogenate in group I/R were significantly higher than those in group S (P<0.05). In group ED, the levels of ALT and AST in tissue bomogenate were significantly lower compared with those in group I/R .The statistical difference was significant (P<0.05).2. The results of kidney functionThe levels of BUN and Cr in kidney serum bomogenate in group I/R were significantly higher than those in group S (P<0.05). In group ED, the levels of BUN and Cr in serum bomogenate were significantly lower compared with those in group I/R .The statistical difference was significant (P<0.05).3. The levels of MDA and SOD in kidney tissueCompared with group S, the levels of tissue bomogenate MDA were significantly increased in group I/R (P<0.05). In group ED, it was significantly lower compared with those in group I/R (P<0.05). The levels of tissue bomogenate SOD were significantly lower in group I/R (P<0.05),In group ED, it was significantly higher compared with those in group I/R (P<0.05).4.The levels of MPO in kidney tissueIn group I/R, the levels of nephridial tissue bomogenate MPO were obviously increased (P<0.05). In group ED, it was significantly lower compared with those in group I/R (P<0.05).5. The concentration of TNF-αin tissueThe levels of TNF-αin liver and nephridial tissue bomogenate in group I/R were significantly higher than those in group S (P<0.05). In group ED, the levels of TNF-αin tissue bomogenate were significantly lower compared with those in group I/R .The difference was significant (P<0.05).6. The results of light microscope:In sham operation group (group S), the structural of hepatic was integrated, hepatic cells were arranged regularly, no significant variability, no necrosis; schemia-reperfusion group (group I/R), With liver cell edema significantly with more space vesicle degeneration, liver sinusoid narrowing extravasated blood, and some have small pieces of liver cell necrosis, the structure of normal liver was disordered; In Edaravone group (group ED), The extent of above-mentioned pathological changes lacking in this group was lessened than that in ischemia-reperfusion group, hepatocellular cloudy swelling, a small number of somewhat necrosis, liver plate structure was basically normal.7. The results of transmission electron microscopeThere was normal ultrastructure in Sham operation group (group S). In the ischemia-reperfusion group (group I/R), mitochondrial swelling was obviously, cristae fracture or disappeared. Quantity of rough endoplasmic reticulum was enlarged more obviously, some of ribosome was disappeared. The Edaravone group (group ED).Mmitochondrion was slightly decreased, rough endoplasmic reticulum was enlarged slightly , ribosome was all preserved.Conclusion:1 Edaravone has protective effects on liver injury and kidney injury induced by hepatic ischemia-reperfusion in rats.2 The mechanisms of the effect of Edaravone on the hepatic I/R are maybe due to the ability of clearing the free radicals,inhibiting lipid peroxidation and then restricting TNF-αresponse indirectly.