The Protective Effects And Mechanisms Of Ulinastatin On Acute Kidney Injury Induced By Sepsis In Rat

Objective:Severe sepsis and sepsis shock are the ultimate manifestations of various infectious diseases, which further development can lead to multiple organ dysfunction syndrome,whose fatality rate as high as 30%-50%,so it is still the major cause of death in critically ill patients. Kidney is one of the most commonly affected organs,which easy to cause acute kidney injury.When sepsis complicated by acute kidney injury,it increase mortality and needs costly medical resources and huge medical expenses. Therefore, early prevention and treatment of Septic acute kidney injury,is significant in protection of renal function.The pathophysiology of AKI which induced by severe sepsis may be associated with the injury of ischemia / reperfusion,inflammatory cascade effect, cell apoptosis and so on.This study investigates the protective effect of ulinastatin against acute renal damage in septic rats,which provide a theoretical basis for clinical application.Methods:120 male SD rats were equally randomized into 5 groups(n=24):health control group(1)sham operation group(2); sepsis group(3),and Ulinastatin postconditioning group(including low dose group(4) and high dose group(5)).Use Cecal ligation-peferation build severe sepsis model. 1,3,5 days after surgery in venous blood samples were drawn, serum NGAL levels, whiletaking kidney specimens.Expressions of NF-κB p65, Caspase-3, Bcl-2 and Bax in kidney were evaluated by immunohistochemical method. Renal pathological morphology examination was also conducted. Using SPSS 21.0 for statistical analysis.Result:At the third and fifth day after the surgery of the rats, the level of serum NGAL of Group 3, 4 and 5 is higher than that of Group 1 and 2 and the comparisons have statistical significance(P<0.05). Meanwhile the level of serum NGAL of these 3 groups is apparently higher than that of Group D and E and the results have statistical significance(P<0.05); the level of serum NGAL of Group 4 is apparently higher than that of Group 5 and the results have statistical significance(P<0.05). The expression of NF-κB p65, Caspase-3, Bcl-2 and Bax of Group 3, 4 and 5 is higher than that of Group 1 and 2, and the comparisons have statistical significance. More specifically, the expression of Group 3 is higher than that of Group 4 and 5 and the results have statistical significance(P<0.05); the expression of Group 5 is lower than that of Group 4 and the results have statistical significance(P>0.05). The levels of serum NGAL are positively correlated with the expression of NF-κB p65, Bax, Bcl-2 and Caspase-3 respectively.Conclusion:Ulinastatin can reduce blood NGAL levels in rats, reduced the expression of NF-κB p65,Bax, Caspase-3 and increase the expression of Bcl-2,it has a protective effect to sepsis-induced acute kindney injury rats,Its mechanism may reduce the systemic inflammatory response, inhibiting apoptosis to protect the kidney tissue.