Effects of quercetin on expression of renal NLRP3 and TLRs in rats with uric acid nephtopathy / 中草药

ABSTRACT

Objective: To investigate the intervention of quercetin on rats with uric acid nephropathy (UAN) and its molecular mechanisms. Methods: Rats were divided into six groups including normal, model, quercetin (25, 50, and 100 mg/kg)-treated, and allopurinol (5 mg/kg)-treated groups. Adenine (100 mg/kg) and ethambutol (250 mg/kg) were ig given to rats once daily for consecutive three weeks to establish UAN model. Quercetin (25, 50, and 100 mg/kg) and allopurinol (5 mg/kg) were initially ig given to UAN rats 1 h after adenine and ethambutol had been given. Rat renal histopathological changes were observed; The levels of uric acid (Sur and Uur), creatinine (Scr and Ucr), and blood urea nitrogen (BUN) in serum and urine were detected; The fractional excretion of uric acid (FEUA) was calculated. Simultaneously, mRNA and protein levels of components of NOD like receptor protein 3 (NLRP3) inflammasomes (NLRP3, ASC, and Caspase-1) and key factors in Toll like receptors (TLRs) signaling pathways (TLR2 and TLR4) were analyzed by RT-PCR and Western blotting methods, respectively. Results: Compared with the model group, quecetin and allopurinol reduced Sur and Scr levels significantly, increased Uur and Ucr excretion in 24 h, and recovered FEUA in UAN rats. Moreover, the mRNA and protein expression of NLRP3, ASC, Caspase-1, TLR2, and TLR4 was up-regulated in UAN rat kidneys, which could be reversed by the treatment of quercetin and allopurinol. Conclusion: These findings suggest that the activated NLRP3 inflammasomes and TLRs signaling pathways could play the causal roles in UAN pathogenesis. Quercetin could ameliorate UAN by regulating NLRP3 inflammasomes and TLRs signaling pathways.