Protective effect of N-acetylcysteine and its mechanism on acute renal injury in septic mice by up-regulating the expression of FLICE inhibitory protein

Abstract

Objective To investigate the effect of N-acetylcysteine (NAC) on acute kidney injury in septic mice by up-regulating the expression of cellular FLICE inhibitory protein (c-FLIP). Methods Thirty male BALB/c mice were randomly divided into the sham operation group (n= 10), sepsis group (n= 10) and NAC group (n= 10). The sepsis mouse model was prepared by cecal ligation and perforation. The sham operation group had the same procedure except for the ligation of puncture caecum. NAC (100 mg/kg) was injected into the tail vein of mice in the NAC group 15 min after operation. The kidney of mice was taken 24 h after the successful modeling, and then pathological changes of kidney tissues were observed under light microscope. The expression of c-FLIP mRNA was detected by quantitative real-time polymerase chain reaction (RT-PCR), and the expression of c-FLIP protein was detected by the Western-blotting method. The above experiment was replicated to observe the mortality of mice within 96 h. Results Compared with the sham operation group, glomerular atrophy, renal tubular epithelial cell deformation, and large amount of interstitial cells and fragments in renal tubule lumen were observed in the sepsis group, while renal tissue lesions in the NAC group significantly reduced. There were significant differences in the renal histopathological injury score, and expressions of c-FLIP mRNA and protein among these three groups (F= 101.400, 31.720, 20.330; all P < 0.05). Further comparison showed that the score of renal histopathological injury in the sepsis group was significantly higher than that in the sham operation group and NAC group (both P < 0.001). Compared with the sham operation group, the c-FLIP mRNA and protein expressions in the sepsis group decreased significantly (both P < 0.05), and the c-FLIP protein expression in the NAC group decreased (P < 0.05). Compared with the sepsis group, the c-FLIP mRNA and protein expressions in the NAC group increased significantly (both P < 0.05). The Kaplan-Meier survival curve showed that the survival of mice was significantly different among these three groups (χ2= 8.806, P= 0.012). Further comparison showed that the survival rate was significantly lower in the sepsis group and NAC group than in the sham operation group (both P < 0.017), while it was significantly higher in the NAC group than in the sepsis group (P < 0.017). Conclusion NAC has a significant protective effect on acute kidney injury in septic mice by up-regulating the c-FLIP expression. Key words: Sepsis; Acute kidney injury; N-acetylcysteine; Cellular FLICE-inhibitory protein; Mice