The Protective Effect Of Rapamycin Blocking MTOR Pathway On Acute Kidney Injury In Sepsis

Obejective:To investigate by inhibiting m TOR signaling pathway the protective function of rapamycin in sepsis induced acute kidney injury.Medthods:We divided Ninety mice into matched group,sepsis group and rapamycin group randomly.Sepsis mice model was prepared by injecting lipopolysaccharide（5mg/kg）diluted with 0.9%sodium chloride solution into the rat body through tail vein.Rapamycin（2mg/kg）diluted with physiological saline was injected into the rat body through tail vein to conduct intervention experiments.Rats in each group were selected to measure indexes at 6th hour,12th hour,24th hour,72th hour and 120th hour.We used the blood from abdominal aorta to test the data of TNF-α,IL-6,IL-10,creatinine,urea nitrogen and NGAL.Then we gathered the urine of rats to detect the data of KIM-1.After kidney specimens taken out,we observed the renal pathology changes,and monitored the expression changes of m TOR m RNA and p70S6K m RNA in kidney tissues.Results:In sepsis group and rapamycin group,from the sixth hour creatinine and urea nitrogen were an upward trend,and It arrives the highest limit on the 72th hour,and then decreased after that.In the statistical,this change in value makes sense contrasted with matched group（P<0.05）.In the rapamycin group,the data contrasted with the sepsis group from the 6^th hour to the 120^th hour were falling（P<0.05）.In the sepsis group and rapamycin group,from 6^th hour to 24^th hour,serum IL-6,IL-10 and TNF-αthan that in the matched group increased,and then the contents gradually declined.In the statistical,this change in value makes sense（P<0.05）.Contrasted with the sepsis group,the data in rapamycin group between the 6^th hour to the 120^th hour were falling（P<0.05）.In the sepsis group and rapamycin group,between the 6^th hour to the 24^th hour,blood NGAL and urine KIM-1 increased than the matched group,and then the contents gradually declined.In the statistical,this change in value makes sense（P<0.05）.Contrasted rapamycin group with the sepsis group,the data from the 6^th hour to the 120^th hour of blood NGAL and urine KIM-1 were falling（P<0.05）.In sepsis group and rapamycin group,from the sixth hour m TOR m RNA and p70S6K m RNA expressions gradually were an upward trend than matched group,and It arrives the highest limit on the 24th hour,and then decreased after that（P<0.05）.Contrasted the rapamycin group with the sepsis group,the expressions between the 6^th hour to the 120^th hour of m TOR m RNA and p70S6K m RNA were relatively declining（P<0.05）.Conclusion:Rapamycin by blocking m TOR/p70S6K signaling pathway in sepsis induced acute kidney injury is protective.It can inhibit inflammatory response,mitigate pathological damage of kidney tissue and enhance renal function.At the same time,NGAL and KIM-1 can play an important role in the early prediction of acute kidney injury in sepsis.