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Mechanism Of Edaravone To Protect Skeletal Muscle From Ischemia Reperfusion Injury

Posted on:2011-11-11Degree:MasterType:Thesis
Country:ChinaCandidate:J Q WeiFull Text:PDF
GTID:2154360308974274Subject:Surgery
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Objective:Ischemia-reperfusion injury is defined as adverse functional,metabolic,or structural changes in ischemic tissue resulting from the restoration of blood flow to the tissue,including swelling,hemorrhage,nece- rosis,and damage from free radicals.The process of reconstructing traumatic exterimity damage,vascularized composite tissue transfer and replantation of amputated limb were suffer from ischemia reperfusion injury.Edaravone,a newly synthesized free-radical scavenger,was approved in Japan for treating acute brain infarction on 2001.The purpose of this study was to investigate whether or not edaravone is effective in reducing ischemia-reperfusion injury in the rabbit's hind-limb skeletal muscle.Methods:Thirty healthy New Zealand rabbits were chosen to set up ischemia-reperfusion models in the left hindlimbs,all of the rabbits were randomly divided into 3 groups:experiment group, control group,sham group.In the experiment group, the femoral artery and vein was exposed and ligated about 3hours, before the blood circulation was restored,the rabbits were given 1.5mg/kg of edaravone through centrial vein of ears,Whereas the saline solution 30ml perfused in control group,then the blood circulation was restored in the limbs and maintained 3 hours.In the sham group the femoral artery and vein was expoesed without ligation.Venous blood about 2ml from the left femoral vein was obtained for analysis of serum level of creatinkinase(CK),lactic acid dehydrogenase(LDH) with automatic biochemistic analysator.The content of endothelin(ET-1) was measured by using radioimmunoassay and nitrogen monoxidum(NO) was detected by using Griess reaction.The quality of tibialis anterior muscles tissues of rabbits about 0.1gram were preversed and 10% homogenate was prepared.The sample were collected to measure content of malondialdehyde(MDA) with the form of thiobarbituric acid reacting substances.The level of superoxidedismutase in skeletal muscle tissue were determined by inhibition of nitroblue tetrazoliumreduction. The tibialis anterior muscles tissue neutrophil content was assessed by measuring the neutrophil-specific enzyme myeloperoxidase (MPO)as an index of neutrophil infiltration.meanwhile water percentage was detected and morphology of tibialis anterior muscles were observed under microscope.RESULTS:All 30 rabbits were involved in the result analysis.The tibialis anterior muscles level of SOD in experiment group were (173.98±12.91)U/g higher than those in control group(87.71±4.46)U/g and lower than in sham group (208.51±10.74)U/g(all P<0.05).The content of MDA,MPO ,the wet/dry weight ratio of tibialis anterior muscles in experimentgroup were(42.81±4.11)μmol/g,(4.28±0.57)U/g,(4.67±0.65)lower than those in control group(74.09±6.21)μmol/g,(8.54±0.74)U/g,(6.09±0.56) (allP<0.05)and higher than those in sham group(29.73±4.17)μmol/g ,(1.66±0.49)U/g(P<0.05).otherwise the wet/dry weight ratio. The serum level of NO in experiment group were(117.22±10.67)μmol/L higher than those in controlgroup(66.23±6.40)μmol/L (P<0.05) and no difference compared with sham group.The content of CK,LDH in serum were (5640±641)U/L,(489.2±44.9)U/L lower than those in control group (7930±623)U/L (593.0±35.9)U/L and higher than in sham group(1985±347)U/L (265.5±23.7)U/L (all P<0.05). The level of ET-1 between experiment group, sham group and control group wasn't significant (P=0.184>0.05).The result of microscopeexamination showed that morphological leision in experiment group was significantly slighter compared with that in control group.Conclusion:Edaravone can decerase the content of free radicals in the skeletal muscle and improve the ischemia-reperfusion induced vascular endothelial function disturbance and it can inhibit the inflammation response and protect the skeletal muscles after ischemia-reperfusion.
Keywords/Search Tags:Edaravone, Free radical, Ischemia-reperfusion injury, Skeletal muscle, Rabbit
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