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薯蓣皂苷和薯蓣皂苷元通过EPHX2减轻肾脏炎症对高原高尿酸血症的保护作用

Protective Effects of Dioscin and Diosgenin on Plateau Hyperuricemia by Attenuating Renal Inflammation via EPHX2.

作者信息

Dang Wanyun, Li Fangyang, Gao Rong, Zhang Cheng, Cheng Hongbo, Wu Zhenhui, Yang Tingyu, Pan Jinchao, Tang Xianglin, Gao Yue

机构信息

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Beijing Institute of Radiation Medicine, Beijing 100859, China.

出版信息

Int J Mol Sci. 2024 Dec 13;25(24):13399. doi: 10.3390/ijms252413399.

DOI:10.3390/ijms252413399
PMID:39769164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11676269/
Abstract

Plateau hyperuricemia is a common disease in the plateau area, and the incidence is much higher than that in the plain area. Dioscin (DIO) and its active metabolite Diosgenin (DG) exert therapeutic effects on hyperuricemia through oxidative stress and inflammation. In this study, DIO and its active metabolite DG were taken as the research objects to explore their therapeutic effects on high-altitude hyperuricemia in rats. To evaluate the therapeutic effect of DIO on the rat model of high-altitude hyperuricemia, the evaluation indexes include blood biochemical indexes, renal histopathology, oil red O staining of the kidney, rat kidney index, and rat renal inflammatory factors. Transcriptomics was used to analyze the control group, model group, and drug-administered group to preliminarily explore the protective mechanism of DIO in rats with high-altitude hyperuricemia. An HK-2 high-altitude hyperuricemia cell injury model was established to verify the therapeutic mechanism of DIO in rats with high-altitude hyperuricemia. Western blot was used to detect the expression of related proteins in renal tissues and cell models. The results showed that DIO and its active metabolite DG regulate renal lipid metabolism through the EPHX2 gene, attenuate renal inflammatory reaction, and then promote the excretion of uric acid and reduce its reabsorption, which ultimately achieves the effect of treating plateau hyperuricemia.

摘要

高原高尿酸血症是高原地区的一种常见疾病，其发病率远高于平原地区。薯蓣皂苷（DIO）及其活性代谢产物薯蓣皂苷元（DG）通过氧化应激和炎症对高尿酸血症发挥治疗作用。本研究以DIO及其活性代谢产物DG为研究对象，探讨它们对大鼠高原高尿酸血症的治疗作用。为评估DIO对大鼠高原高尿酸血症模型的治疗效果，评估指标包括血液生化指标、肾脏组织病理学、肾脏油红O染色、大鼠肾脏指数和大鼠肾脏炎症因子。采用转录组学分析对照组、模型组和给药组，初步探讨DIO对高原高尿酸血症大鼠的保护机制。建立HK-2高原高尿酸血症细胞损伤模型，验证DIO对高原高尿酸血症大鼠的治疗机制。采用蛋白质免疫印迹法检测肾脏组织和细胞模型中相关蛋白的表达。结果表明，DIO及其活性代谢产物DG通过EPHX2基因调节肾脏脂质代谢，减轻肾脏炎症反应，进而促进尿酸排泄并减少其重吸收，最终达到治疗高原高尿酸血症的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6734/11676269/656a20549747/ijms-25-13399-g010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6734/11676269/6d63ab580519/ijms-25-13399-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6734/11676269/2985a42b1c9b/ijms-25-13399-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6734/11676269/656a20549747/ijms-25-13399-g010.jpg

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