Department of Nephrology, The Third Affiliated Hospital, Southern Medical University, Guangzhou, People's Republic of China.
Department of Nephrology, The First Affiliated Hospital of University of South China, Hengyang, People's Republic of China.
Drug Des Devel Ther. 2020 Jun 8;14:2221-2233. doi: 10.2147/DDDT.S247091. eCollection 2020.
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.
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.
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.
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.
高尿酸血症是肾脏损害的独立危险因素，并可促进慢性肾脏病（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，并阐明其相关机制。
通过每日口服腺嘌呤和氧嗪酸钾混合物，连续 3 周建立 HN 大鼠模型。24 只大鼠被分为 4 组：假手术组、假手术+RGTZ 组、HN 组和 HN+RGTZ 组。
RGTZ 治疗可有效保护肾功能，降低尿微量白蛋白，并抑制 HN 大鼠模型中的间质纤维化和巨噬细胞浸润。RGTZ 治疗还抑制了 TGF-β和 NF-κB 通路的激活，降低了纤维连接蛋白、胶原 I、α-SMA、波形蛋白、MCP-1、RANTES、TNF-α和 IL-1β的表达，增加了 HN 大鼠肾脏中 E-钙黏蛋白的表达。此外，RGTZ 治疗还能维持 HN 大鼠肾脏中 OAT1 和 OAT3 的表达。
RGTZ 通过抑制 TGF-β信号通路、抑制上皮间质转化、减少炎症反应和维持尿酸转运体的表达来降低血尿酸水平，从而减轻 HN 的进展。
