Protective Effects Of Edaravone On Hepatic Injury Induced By Ischemic Stroke In Rat

OBJETIVES To investigate the liver damage induced by cerebral ischemia and the extents of damage on liver function,and explore the protective effects of edaravone on cerebral ischemia-induced liver damage model and its mechanism,in order to provide some references for clinical intervention in the treatments of liver injury.METHODS Rats weighing 260-300 g were randomly divided into 4 groups: control + saline(CN),shame+ saline(SN),MCAO+saline(MN)and MCAO+Edaraone(ME),each group included 8 rats.The middle cerebral artery occlusion(MCAO)established the model of focal cerebral ischemia was performed by modified Longa suture method.CN: only treated with saline at 3mg/kg·iv.;SN: only cut the neck skin and separated the blood vessels without inserting the bolt,then treated with saline at 3mg/kg·iv.MN: tail vein injection of edaravone at 3mg/kg followed MCAO.ME: tail vein injection of edaravone at 3mg/kg followed MCAO.Saline or edaravone in each group were pumped through the tail vein within 30 min.To kill the animals at 6 hours after ischemia.Observing histological and ultrastructural changes of brain and testing the level of Serum ALB,ALT,AST,and Ca2+ levels.Serum tumor necrosis factor-?(TNF-?),interleukin-6(IL-6)and mitochondrial superoxide dismutase(SOD),malondialdehyde(MDA)were measured.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase d UTP nick-end labeling(TUNEL)assay.Histopathological changes of cells were observed by HE staining in liver tissue.RESULTS The rat model of ischemic stroke was successfully established: all rat's score of Zea-Longa was 0 points before experiment.After the experiment,the rats in group CN and SN were scored 0 points,and the scores of MN group and ME group were 1-3points.The TTC staining MN group and ME group of brain tissue sections showed partial pale ischemic area after 6 hours.The serum results show: compared with SN,the levels of ALT,AST and the contents of MDA,TNF-?,MPO,IL-6 were increased in MN and ME group,the contents of ALB ? Ca2+ and T-SOD were decreased,these have significant difference(P<0.05).However,Compared with MN,the levels of ALT,AST and the contents of MDA,TNF-?,MPO,IL-6 were decreased in ME,the contents of ALB and SOD were increased,these have significant difference(P<0.05).But compared with MN,Ca2+ in ME have no significant difference(P>0.05).The apoptosis index of liver cells in MN and ME were increased compared with SN,decreased in ME compared with MN.Hepatocytes of the MN showed hepatocellular dysplasia,obvious vacuolar changes,necrotic lesions,hepatic lobular structure disorder,hilar congestion,inflammatory cell infiltration,nuclear staining deepening indicated by histopathological analysis.Fatty infiltration changes,light vacuolar change,scattered inflammatory cells and mild hepatocyte necrosis can be observed in ME.CONCLUSION In this study,we established ischemic stroke rat mode successfully,and found that cerebral infarction can cause liver damage after 6h,the mechanism may be associated with hypoxia,hypoxia caused by increased oxygen free radical release,abnormal energy metabolism and intracellular Ca2+ overload;while a large number of inflammatory mediators and cytokines released into the blood,activation of apoptosis pathway,and further cause liver damage.This study also shows that Edaravone can reduce oxidative stress by reducing oxygen free radicals,reduce cell membrane peroxidation,reduce the expression of TNF-?,MPO,IL-6 and other inflammatory factors,reduce the inflammatory response,thus reduce liver damage.