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高尿酸血症及其相关疾病:发病机制与治疗进展。

Hyperuricemia and its related diseases: mechanisms and advances in therapy.

机构信息

Sports Medicine Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, 515041, China.

Institute of Sports Medicine, Shantou University Medical College, Shantou, 515041, China.

出版信息

Signal Transduct Target Ther. 2024 Aug 28;9(1):212. doi: 10.1038/s41392-024-01916-y.

DOI:10.1038/s41392-024-01916-y
PMID:39191722
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11350024/
Abstract

Hyperuricemia, characterized by elevated levels of serum uric acid (SUA), is linked to a spectrum of commodities such as gout, cardiovascular diseases, renal disorders, metabolic syndrome, and diabetes, etc. Significantly impairing the quality of life for those affected, the prevalence of hyperuricemia is an upward trend globally, especially in most developed countries. UA possesses a multifaceted role, such as antioxidant, pro-oxidative, pro-inflammatory, nitric oxide modulating, anti-aging, and immune effects, which are significant in both physiological and pathological contexts. The equilibrium of circulating urate levels hinges on the interplay between production and excretion, a delicate balance orchestrated by urate transporter functions across various epithelial tissues and cell types. While existing research has identified hyperuricemia involvement in numerous biological processes and signaling pathways, the precise mechanisms connecting elevated UA levels to disease etiology remain to be fully elucidated. In addition, the influence of genetic susceptibilities and environmental determinants on hyperuricemia calls for a detailed and nuanced examination. This review compiles data from global epidemiological studies and clinical practices, exploring the physiological processes and the genetic foundations of urate transporters in depth. Furthermore, we uncover the complex mechanisms by which the UA induced inflammation influences metabolic processes in individuals with hyperuricemia and the association with its relative disease, offering a foundation for innovative therapeutic approaches and advanced pharmacological strategies.

摘要

高尿酸血症(HUA)的特征是血清尿酸(SUA)水平升高,与痛风、心血管疾病、肾脏疾病、代谢综合征和糖尿病等一系列疾病有关。HUA 显著降低了患者的生活质量,其患病率在全球呈上升趋势,尤其是在大多数发达国家。UA 在生理和病理环境中具有多方面的作用,如抗氧化、促氧化、促炎、调节一氧化氮、抗衰老和免疫作用。循环尿酸水平的平衡取决于产生和排泄之间的相互作用,这是由各种上皮组织和细胞类型中的尿酸转运蛋白功能协调的微妙平衡。虽然现有研究已经确定了 HUA 参与了许多生物过程和信号通路,但将 UA 水平升高与疾病病因联系起来的确切机制仍有待充分阐明。此外,遗传易感性和环境决定因素对 HUA 的影响需要进行详细和细致的检查。本综述汇集了全球流行病学研究和临床实践的数据,深入探讨了尿酸转运蛋白的生理过程和遗传基础。此外,我们揭示了 UA 诱导的炎症如何影响 HUA 个体代谢过程的复杂机制及其与相关疾病的关联,为创新的治疗方法和先进的药物策略提供了基础。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae03/11350024/a0d5732c1501/41392_2024_1916_Fig2_HTML.jpg
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