Abstract:

Abstract:Objective  To investigate the expression of nucleotide-binding and oligomerization domain (NOD)-like receptor 3 (NLRP3) in kidney tissue of mice with acute renal failure induced by aristolochic acid-1 (AA) and its significance,and to clarify the role of NLRP3 in the development of AA-induced nephropathy.Methods Male ICR mice were randomly divided into control group and AA group.The mice in AA group received AA by gavage at doses of 50,100 and 200 mg?kg-1 daily and lasted for 3 d.There were 16 mice in  each group.4 and 8 d after administration,8 mice of each group were killed respectively and urinary and serum were collected to detect 24 h urinary protein,serum creatinine and urea nitrogen levels.The IL-1β and IL-18 levels in serum were measured by ELISA kits.Moreover,real-time PCR was used to examine the mRNA expression of NLRP3 in kidney tissue.Results Compared with control group,the  24 h urinary protein,serum creatinine and serum BUN of the mice in AA  group were significantly decreased 4 and 8 d after administration (P<0.05),and the mice in 200 mg?kg-1 AA group were death at day 7. Compared with control group,the IL-1β and IL-18 levels in serum of the mice in AA group were significantly increased (P<0.05),and the mRNA expression of NLRP3 in kidney tissue was also up-regulated (P<0.05).Moreover,the expression level of NLRP3 in 200  mg/kg AA group was significantly higher than that in 50 mg/kg AA group (P<0.05).Conclusion The up-regulation of NLRP3 in kidney tissue of the mice may participate in the pathological process of actue renal failure induced by AA.

Key words: aristolochic acid, acute renal injury, nucleotide-binding and oligomerization domain like receptor, cytokines