Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China.
J Immunol Res. 2021 Nov 1;2021:5151168. doi: 10.1155/2021/5151168. eCollection 2021.
Uric acid is an effective antioxidant. Oxidized low-density lipoprotein (ox-LDL) is derived from circulating LDL and promotes atherosclerosis. The Keap1-Nrf2-ARE pathway is a key body pathway involved in protection against internal and external oxidative damages. The role of uric acid on vascular endothelial function damaged by ox-LDL, and its effect on the Keap1-Nrf2-ARE pathway has not been fully explored. HUVECs were treated with different concentrations of uric acid and ox-LDL to explore the effect of uric acid in vitro. Cell phenotype was determined by cytometry and Western blot. Nuclear translocation of Nrf2 was determined by immunofluorescence. Coimmunoprecipitation was used to determine the level of Nrf2 ubiquitination. A microfluidic device was used to mimic the vascular environment in the body, and the level of mRNA levels of inflammatory factors was determined by RT-PCR. The findings of this study show that suitable uric acid can significantly reduce endothelial damage caused by ox-LDL, such as oxidative stress, inflammation, and increased adhesion. In addition, uric acid reduced Nrf2 ubiquitination and increased nuclear translocation of Nrf2 protein, thus activating the Keap1-Nrf2-ARE pathway and playing a protective role. Interestingly, the effects of UA were significantly inhibited by administration of Brusatol, an inhibitor of Nrf2. In summary, suitable concentrations of uric acid can alleviate the oxidative stress level of endothelial cells through Nrf2 nuclear translocation and further protect cells from damage.
尿酸是一种有效的抗氧化剂。氧化型低密度脂蛋白（ox-LDL）来源于循环 LDL，并促进动脉粥样硬化。Keap1-Nrf2-ARE 通路是一种重要的内源性抗氧化防御系统。尿酸对 ox-LDL 损伤的血管内皮功能的作用及其对 Keap1-Nrf2-ARE 通路的影响尚未完全阐明。本研究采用不同浓度尿酸和 ox-LDL 处理人脐静脉内皮细胞（HUVECs），体外探讨尿酸的作用。通过流式细胞术和 Western blot 检测细胞表型。通过免疫荧光检测 Nrf2 的核转位。通过 co-IP 检测 Nrf2 的泛素化水平。采用微流控装置模拟体内血管环境，通过 RT-PCR 检测炎症因子 mRNA 水平。本研究结果表明，适量尿酸可显著减轻 ox-LDL 引起的内皮损伤，如氧化应激、炎症和黏附增加。此外，尿酸降低了 Nrf2 的泛素化，增加了 Nrf2 蛋白的核转位，从而激活了 Keap1-Nrf2-ARE 通路并发挥保护作用。有趣的是，UA 的作用被 Nrf2 抑制剂 Brusatol 显著抑制。综上所述，适量尿酸可通过 Nrf2 核转位降低内皮细胞氧化应激水平，进而保护细胞免受损伤。
