| Objective: To observe the effect of rapamycin on acute renal injury in sepsis rats and explore its possible mechanisms.Methods: Thirty six healthy male SD rats were randomly divided into three groups: sham operation group(Group C,the cecum was only dragged out of the abdominal cavity,but not ligated and punctured),rapamycin group(Group R,the cecum was back to the abdominal cavity without ligated and punctured,and rapamycin was injected into the abdominal cavity after abdominal closure of 6mg / kg),sepsis group(Group S,the cecum was ligated and punctured),Sepsis animal model and sepsis + rapamycin intervention group(SR group,6 mg / kg of rapamycin was injected intraperitoneally after cecal ligation and puncture).24 hours after the operation,the upper serum of the vena cava blood was centrifuged to detect the levels of creatinine(crea),urea nitrogen(BUN)and serum cysteine proteinase inhibitor C(Cys-C);the levels of tumor necrosis factor(TNF-?)and interleukin-1 ?(IL-1 ?)in the renal tissue were detected by ELISA;the pathological changes of the renal tissue were observed by HE staining and the pathological scores of the renal tissue were made.Western blot was used to detect the levels of lc3 b,p62 protein and m TOR,4ebp1,P70S6 K phosphorylation protein.Results:1.HE staining showed that the structure of glomeruli in the sham operation group and rapamycin group was normal,the lumen of renal tubules was integrity,and there was no obvious inflammatory cell infiltration in renal interstitium;in the sepsis group,the glomeruli capillary was dilated and congested,the epithelial cells of renal tubules were edematous,vacuolated,and a large number of inflammatory cells were infiltrated in renal cortex and interstitium;in the sepsis + rapamycin intervention group,the glomeruli and renal tubules were infiltrated and the pathological changes of renal interstitium were lighter than those of sepsis group.2.Compared with the sham operation group,the renal tissue injury score of sepsis group was significantly higher(P < 0.05);compared with sepsis group,the renal tissue injury score of sepsis +rapamycin intervention group was significantly lower(P < 0.05).3.There was no significant difference in crea,BUN and Cys-C levels between sham operation group and rapamycin group(P > 0.05);crea,BUN and Cys-C levels in sepsis group were significantly higher than those in sham operation group and rapamycin group(P <0.05);crea,bun and Cys-C levels in sepsis + rapamycin intervention group were significantly lower than those in sepsis group(P < 0.05).4.There was no significant difference in the detected level of TNF-? and IL-1 ? between the sham operation group and rapamycin group(P > 0.05);TNF-? and IL-1 ? in sepsis group were significantly higher than those in sham operation group and rapamycin group(P <0.05);compared with sepsis group,TNF-? and IL-1 ? in sepsis + rapamycin intervention group decreased(P < 0.05).5.Compared with the sham operation group,the expression of lc3 b protein in sepsis group was higher than that in sham operation group,while the expression of p62 protein in rapamycin group was lower than that in sham operation group;compared with sepsis group,the expression of lc3 b protein in sepsis + rapamycin group was significantly higher and the expression of p62 protein was down regulated(P < 0.05).6.Compared with sham operation group,m TOR,4ebp1 and P70S6 K phosphorylation protein levels in the other three groups decreased(P < 0.05).The expression of m TOR,4ebp1 and P70S6 K phosphorylated protein in rapamycin group was lower than that in sham operation group(P < 0.05).Compared with sepsis group,the expression of m TOR,4ebp1 and P70S6 K phosphorylated protein in sepsis + rapamycin group was down regulated(P < 0.05);Conclusion:Intraperitoneal injection of rapamycin in sepsis rats can reduce the degree of renal injury and the pathological changes of renal tissues.The analysis may be related to the inhibition of m TOR signaling pathway by rapamycin to promote renal autophagy. |
PDF Full Text Request