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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 evaluate whether the combination of Uremic clearance granule with Alprostadil is superior to Alprostadil alone for CRF. Methods: Relevant RCTs were searched through March 2019. Data were analyzed by Stata 15.0. Results: Nine articles involving 726 patients were enrolled in this study. Meta-analysis showed that the total effective rate [OR = 3.68 (2.44, 5.55), P < 0.001], Scr [SMD = -2.34 (-3.49, -1.19), P < 0.001], BUN [SMD = -1.80 (-2.73, -0.87), P < 0.001], Ccr [SMD = 0.71 (0.44, 0.97), P < 0.001] were better in the experimental group. But there were no significant difference in UA, CysC, 24h-Upro and incidence of adverse reactions (all P > 0.05) between two groups. No serious adverse reactions were found. Conclusions: The effect of the integrated medicine on CRF was better than Alprostadil alone. Uremic clearance granule is safe and has no obvious adverse reactions.