Study Of Injury And Protection On Liver And Kidney Of Rat After Amputation

Background and Objective:When the organism suffers the irritations such as serious trauma,operation,shock,it will automatically respond to the injury,and the excessive defenses probably hurt itself,especially,the organs of heart,brain,liver and kidney are damaged critically.Kidney is a important organ which evacuates toxinum out of the body,regulate water-electrolyte balance,and it is an endocrine organs.Liver is very important in the aspects of composition and metabolism.But they are very easily harmed on the condition of stress.Clinically,many patients after operations have acute renal failure,once appeared,mortality rate of these patients is so high.The mechanism of acute kidney injury following trauma is very complicated,it is very difficult to diagnose early and to take precautionary measures effectively.The hepatic lesion is also found after operation and empyrosis,the mechanism is in nubibus,so we make the model of amputation-rats to study the mechanism of the injury of liver and kidney,to study the biological parameter of liver and kidney to diagnosis in early stage,to study the role of hydrogen sulfide(NaHS), propargylglycine(PPG),tacrolimus(FK506) and aldactone in the process of injury.Our experiment is divided into two parts.Firstly,we explore the role of the neutrophils and inflammatory cytokines,oxidant-antioxidant system,aldosterone (ALD) and the level of endogenous hydrogen sulfide(H₂S)/cystathionine-γ-lyase (CSE) system,calcineurin,KIM-1 of kidney.Secondly,we are to ascertain the mitochondria energy metabolism of liver and kidney after intervention in amputation-rats.Methods:In the first part,ninty-one male Wistar rats were divided into 13 groups at random:Group normal,Group 1h after trauma,Group 2h,Group 4h,Group 6h,Group 12h,Group 24h,Group 48h,Group 72h;and 4 groups with interventions:group-NaHS,group- PPG,group-FK506,group-aldactone.The plasma levels of H₂S,MPO,MDA,ALD,NO,Angâ…¡,IL-6,KIM-1 were measured in each group.The level of KIM-lin kidney and MPO,MDA,CSE.and CnA-αwere detected in liver and kidney.In the second part,48 SD rats were divided into Group normal,Group 6h,4 groups with interventions:group-NaHS,group-PPG,group-FK506,group-aldactone. The respiratory control ratio,membrane potential and ATP enzymatic activity of were detected in mitochondria of liver and kidney.Results:Compared with Group normal,histopathologic results indicated the injury of liver and kidney following amputation.It indicated congestion of tissue,dropsy of cell,the damage of group 6h is the most serious.Compared with Group normal,the levels of MPO,MDA,IL-6,Angâ…¡in plasma increased and the levels of Cr,ALT,AST,H₂S,ALD and NO in plasma decreased;the levels of plasma and renal KIM-1 rose sharply;the levels of MPO,MDA increased after trauma in liver and kidney,inversely CSE activity and ALD level in kidney were descendent.Following surgery CnA-αmRNA inceased in both liver and kidney.Compared with Group 6h,the plasma levels of Cr,NO,ALD,Angâ…¡,MPO and H₂S increased significantly by given NaHS,but the levels of MDA,KIM-1 and IL-6 decreased.The damages of pathology lightened slightly.The levels of MDA,MPO and KIM-1 decreased significantly in kidney,and the levels of CSE,ALD and CaN of kidney increased.The levels of MDA and MPO decreased significantly in liver,and the levels of CSE and CaN of liver increased significantly.The respiratory control ratio,membrane potential and ATP enzymatic activity of were increased significantly in mitochondria of liver and kidney,and they were increased some degrees by given NaHS.The changes of group-FK506,group-aldactone were similar to the group-NaHS, but the group-PPG was contrary in major targets.Conclusions:Amputation can induce acute injury of liver and kidney.The injury is the most serious in 6 hours after trauma.KIM-1 is possible an sensitive biomarker of AKI.The mechanism may be involved in the activating of neutrophil and inflammatory cytokines,excess oxidative stress,the imbalance of oxidant-antioxidant system,high secreting of aldosterone.The down-regulation of endogenous H₂S/CSE system,up-regulation of CnA- a may play an important role in the progress of liver and kidney injury.NaHS,FK-506,aldactone may protect liver and kidney after amputation.PPG may make the injury more seriously after operation.