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Objective Uric acid (UA) activates the NLRP3-ASC-caspase-1 axis and triggers cascade inflammatory that leads to hyperuricemic nephropathy and hyperuricemia-induced renal tubular injury. The original study aims to verify the positive effects of the traditional Chinese medicinal formula Shizhifang (SZF) on ameliorating the hyperuricemia, tubular injury, and inflammasome infiltration in the kidneys of hyperuricemic lab rats. Method Twenty-eight male Sprague-Dawley rats were divided into four groups: control group, oxonic acid potassium (OA) model group, OA + SZF group, and OA + Allopurinol group. We evaluated the mediating effects of SZF on renal mitochondrial reactive oxygen species (ROS) and oxidative stress (OS) products, protein expression of NLRP3-ASC-caspase-1 axis, and downstream inflammatory factors IL-1β and IL-18 after 7 weeks of animals feeding. Result SZF alleviated OA-induced hyperuricemia and inhibited OS in hyperuricemic rats (P < 0.05). SZF effectively suppressed the expression of gene and protein of the NLRP3-ASC-caspase-1 axis through accommodating the ROS-TXNIP pathway (P < 0.05). Conclusion Our data suggest that SZF alleviates renal tubular injury and inflammation infiltration by inhibiting NLRP3 inflammasome activation triggered by mitochondrial ROS in the kidneys of hyperuricemic lab rats.

increasing uric acid (ua) could induce renal tubular epithelial cell (NRK-52E) injury. However, the specific mechanism by which UA induces renal tubular epithelial cell injury remains unknown. It was hypothesized that UA induces renal tubular epithelial cell injury through reactive oxygen species (ROS) and the Never in mitosis gene A (NIMA)-related kinase 7 (NEK7)/NLR family pyrin domain containing 3 (NLRP3) signaling pathway. TUNEL assay and flow cytometry were applied to measure apoptosis, and the results of the present study showed that UA treatment induced apoptosis of NRK-52E cells in a concentration-dependent manner. Western blotting was performed to determine the expression levels of cleaved caspase-3, Bax and Bcl-xl, it was found that levels were significantly increased after UA treatment in NRK-52E cells. ROS and apoptosis were predominantly induced in NRK-52E cells and there was an association between roS and apoptosis. Enhanced expression of NEK7, NLRP3, apoptosis-associated speck-like and caspase-1 were observed in NRK-52E cells treated with ua. The roS inhibitor, n-acetyl-l-cysteine, exerted a protective effect on the UA-induced apoptosis of tubular epithelial cells by reducing excess roS production, which significantly inhibited NEK7 and NLRP3 inflammasome activation. These results indicated that UA activates ROS and induces apoptosis of NRK-52E cells. The mechanism might be related to the regulation of the NEK7/NLRP3 signaling pathway.

Objective To explore the effect and mechanism of ShiZhiFang on uric acid metabolism. Methods 40 rats were divided into normal group, model group, ShiZhiFang group, and benzbromarone group. The hyperuricemic rat model was induced by yeast gavage at 15 g/kg and potassium oxonate intraperitoneal injection at 600 mg/kg for two weeks. During the next two weeks, ShiZhiFang group rats were given ShiZhiFang by gavage, and benzbromarone group rats were given benzbromarone by gavage. The serum uric acid, creatinine, blood urea nitrogen, XOD activity, urinary uric acid, urinary β2-MG, and histopathological changes were observed in the rats of each group after treatment. Results The hyperuricemic model was established successfully and did not show the increase of serum creatinine and blood urea nitrogen. Compared with the model group, the serum uric acid, serum XOD activity, and urinary β2-MG were significantly decreased (p < 0.05), and 24 h urinary uric acid excretion was significantly decreased (p < 0.01) in ShiZhiFang group, whereas the two treatment groups were of no statistical significant in above indicators (p > 0.05); renal histopathology showed that the lesions in two treatment groups were reduced compared to the model groups. The gene and protein expression of uric acid anion transporters rOAT1 and rOAT3 in the kidney was significantly higher than that in model group (p < 0.01). Conclusion The model is suitable for the study of primary hyperuricemia. The mechanisms of ShiZhiFang on uric acid metabolism in hyperuricemic rats may be involved in reducing the activity of serum XOD and promoting the transcription and expression of rOAT1 and rOAT3 in the kidney.