This study is designed to explore the mechanism by which long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays a pathogenic role in uric acid nephropathy (UAN). The expressions of ANRIL, miR-122-5p, BRCA1-BRCA2-containing complex subunit 3 (BRCC3) and NOD-like receptor protein 3 (NLRP3) were determined in UAN patients and uric acid-treated HK-2 cells by qRT-PCR. Protein levels of BRCC3 and NLRP3 were examined by western blot. The levels of inflammatory cytokines were quantified by ELISA. CCK-8 assay was used to assess cell viability. Apoptosis was detected by Annexin V-FITC/PI double-labeled flow cytometry and TUNEL assay. The interaction between ANRIL, miR-122-5p and BRCC3 were studied using luciferase reporter assay. The role of ANRIL in renal injury was evaluated in experimental rats. ANRIL and BRCC3 were highly expressed while miR-122-5p was down-regulated in serum of UAN patients and uric acid-treated tubular epithelial cells. Luciferase reporter assay and in vitro rescue experiment confirmed that ANRIL promoted NLRP3 inflammasome activation by up-regulating BRCC3 expression via sponging miR-122-5p. Furthermore, in vivo experiment validated that knockdown of ANRIL alleviated renal injury of UAN rats. ANRIL exerted pathogenic effect in UAN to promote NLRP3 inflammasome activation via miR-122-5p/BRCC3 axis.

本研究旨在探讨INK4基因座（ANRIL）中长非编码RNA（lncRNA）反义非编码RNA在尿酸肾病（UAN）中起致病作用的机制。通过qRT-PCR测定UAN患者和经尿酸处理的HK-2细胞中ANRIL，miR-122-5p，含BRCA1-BRCA2的复合亚基3（BRCC3）和NOD样受体蛋白3（NLRP3）的表达。 。通过蛋白质印迹检查BRCC3和NLRP3的蛋白水平。通过ELISA定量炎性细胞因子的水平。使用CCK-8测定来评估细胞生存力。通过膜联蛋白V-FITC / PI双标记流式细胞仪和TUNEL测定法检测凋亡。使用荧光素酶报告基因分析研究了ANRIL，miR-122-5p和BRCC3之间的相互作用。在实验大鼠中评估了ANRIL在肾损伤中的作用。在UAN患者的血清和尿酸治疗的肾小管上皮细胞中，miR-122-5p的表达下调了ANRIL和BRCC3的表达。萤光素酶报告基因测定和体外抢救实验证实，ANRIL通过海绵状miR-122-5p上调BRCC3表达来促进NLRP3炎性体活化。此外，体内实验验证了ANRIL的敲低减轻了UAN大鼠的肾脏损伤。ANRIL在UAN中发挥致病作用，以通过miR-122-5p / BRCC3轴促进NLRP3炎性小体活化。