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The Mechanism And Protection Of The Liver & Kidney Injury And Mitochondrion Injury Induced By The Total Hepatic Ischemia-reperfusion In Rats

Posted on:2010-08-08Degree:MasterType:Thesis
Country:ChinaCandidate:Y W ChenFull Text:PDF
GTID:2144360275452875Subject:Geriatrics
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Background and Objective:The total hepatic ischemia-reperfusion is unavoidable in liver operation and liver transplantation.Recently,people pay more attention to the ischemia-reperfusion injury and carry out a series of relative researches.The total hepatic ischemia-reperfusion injury indeed brings serious damage to the other organs.Lots of mediators of inflammation includes acidic metabolites,endotoxin,oxygen redicals,tumor necrosis factor pour to lung,and may lead to acute lung injury or respiratory failure.In kidney,they may lead to renal insufficiency.The interruption of portal vein blood can increase the pressure of portal vein,and the latter may lead to gastrointestinal tract injury, microcirculation disturbance,mucous membrane edema,hemorrhage or necrosis. The most dangerous endotoxemia and displacement of intestinal bacteria may threaten the patients life.Kidney is a vital organ in metabolism,whose function affect patient's survival rate after operation.We have established the model of total hepatic ischemia -repersusion by surgery to observe inflammatory reaction, lipid peroxidation,H2S/CSE system,CaN signal transduction path in the reperfusion injury,and to search the effective intervention method.Method:We have established the model of total hepatic ischemia-repersusion by surgery.First,eighty eight Wistar rats were divided into the control group, ischemia 20min,20min+6h,20min+12h,20min+24h,20min+48h,20min+72h; ischemia 40min,40min+6h,40min+72h,and eight rats in every group.Second, ninety six Wistar rats were divided into twelve groups,eight rats in every group: FK506 control,spironolactone control,Medrlylprednisolone control,NaHS control;20min+6h+FK506,20min+6h+ spironolactone,20min+6h+MP,20min+6h+ NaHS;40min+6h+spironolactone,40min+6h+ MP,40min+72h+ spironolactone,40min+72h+ MP.The H2S,MDA,AngⅡ,ALD,TNF-α,CysC,ALT,BuChE in blood,and the activity of CSE,the level of ICAM-1,NF-κB,CaN in tissue are determinded.Optical microscope was used to observe the pathological change of the liver and kidney.Lastly,we determined the respiratory control rate(RCR),P/O ratio,membrane potential and ATPase activity of mitochondrion to research the mechanism of liver,kidney and mitochondrion injury after ischemia-reperfusion.Result:The results of the first part were as follows:Compared to the control group,the level of ALT,CysC,TNF-α,MDA,AngⅡin blood,KIM-1 in kidney, ICAM-1,NF-κB in liver were significantly increased after ischemia and reperfusion,and reached the peak in the 20min+6h group.The BuChE level began to decrease after ischemia and reperfusion with the minimus in the 20min+24h group.The level of ALD in plasma,ICAM-1,NF-KB in kidney reached the peak in 20min group,and decreased after reperfusion.The level of ALD in liver increased after ischemia,and reached the peak in the 20min+2h group.The H2S show a fluctuant change.The activity of CSE enzyme were decreased after ischemia,but the activity began to recovery after reperfusion. After the intervention of FK506,spironolactone,MP,NaHS,the level of TNF-α,MDA in plasma,KIM-1 in kidney,ICAM-1,NF-κB in tissue were significantly lower.The level of AngⅡdecreased and the ALD in plasma increased in the spironolactone group.The level of CaN were decreased in the four intervention groups.The level of H2S and the activity of CSE enzyme were higher in the NaHS group.MP can affect the ALT and BuChE in plama.The results of the last part were as follows:After total hepatic ischemia reperfusion, the activity of the ATPase and the RCR,P/O and membrane potential were significantly lower.After the intervention of the four medicines,the respiratory function and ATPase activity were improved under the different degrees.Conclution:The total hepatic ischemia-reperfusion may induce the injury of the liver and kidney,and the most serious damage happened in the reperfusion 6h. The mechanism may be involved the activating of inflammation reaction,lipid peroxidation,H2S/CSE system,CaN signal transduction path.FK506,spironolactone,MP,NaHS may develop the protection by the involved machnism.
Keywords/Search Tags:reperfusion injury, calcineurin, aldosterone, angiotension, hydrogen sulfide
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