Purpose: Hyperuricemia is an independent risk factor for renal damage and can promote the progression of chronic kidney disease (CKD). In the present study, we employ a rat model to investigate the effects of rosiglitazone (RGTZ), a peroxisome proliferator-activated receptor-gamma agonist, on the development of hyperuricemic nephropathy (HN), and we elucidate the mechanisms involved.
Methods: An HN rat model was established by oral administration of a mixture of adenine and potassium oxonate daily for 3 weeks. Twenty-four rats were divided into 4 groups: sham treatment, sham treatment plus RGTZ, HN, and HN treated with RGTZ.
Results: Administration of RGTZ effectively preserved renal function, decreased urine microalbumin, and inhibited interstitial fibrosis and macrophage infiltration in a rat HN model. RGTZ treatment also inhibited TGF-β and NF-κB pathway activation, decreased expression of fibronectin, collagen I, α-SMA, vimentin, MCP-1, RANTES, TNF-α, and IL-1β, and increased E-cadherin expression in the kidneys of HN rats. Furthermore, RGTZ treatment preserved expression of OAT1 and OAT3 in the kidney of HN rats.
Conclusion: RGTZ attenuates the progression of HN through inhibiting TGF-β signaling, suppressing epithelial-to-mesenchymal transition, reducing inflammation, and lowering serum uric acid levels by preserving expression of urate transporters.

Keywords: hyperuricemic nephropathy, peroxisome proliferator-activated receptor-gamma, rosiglitazone, renal fibrosis, epithelial-to-mesenchymal transition, inflammation



中文翻译：

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用 PPAR-γ 激动剂治疗可预防大鼠模型中的高尿酸血症肾病。

目的：高尿酸血症是肾损害的独立危险因素，可促进慢性肾脏病（CKD）的进展。在本研究中，我们采用大鼠模型来研究过氧化物酶体增殖物激活受体-γ 激动剂罗格列酮 (RGTZ) 对高尿酸血症肾病 (HN) 发展的影响，并阐明所涉及的机制。
方法：通过每日口服腺嘌呤和氧酸钾混合物连续3周建立HN大鼠模型。24只大鼠分为4组：假治疗组、假治疗组加RGTZ组、HN组和HN组加RGTZ组。
结果：在大鼠 HN 模型中，RGTZ 的给药有效地保留了肾功能，减少了尿微量白蛋白，并抑制了间质纤维化和巨噬细胞浸润。RGTZ 治疗还抑制 TGF-β 和 NF-κB 通路激活，降低纤连蛋白、胶原蛋白 I、α-SMA、波形蛋白、MCP-1、RANTES、TNF-α 和 IL-1β 的表达，并增加 E-钙粘蛋白的表达。 HN 大鼠的肾脏。此外，RGTZ 治疗保留了 HN 大鼠肾脏中 OAT1 和 OAT3 的表达。
结论： RGTZ 通过抑制 TGF-β 信号传导、抑制上皮间质转化、减少炎症和通过保留尿酸盐转运蛋白的表达降低血清尿酸水平来减弱 HN 的进展。

关键词：高尿酸血症肾病，过氧化物酶体增殖物激活受体-γ，罗格列酮，肾纤维化，上皮间质转化，炎症