Background

Chronic renal allograft dysfunction (CRAD) is the main condition affecting the long-term survival of renal allografts. Rosiglitazone, which is a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, has been shown to exert antifibrotic and anti-inflammatory effects on some renal diseases. The present paper investigates the effect of rosiglitazone on CRAD using a murine model.

Methods

The CRAD group received classical orthotopic F344-Lewis kidney transplantation. The treatment group was treated with rosiglitazone for 12 weeks following renal transplantation. The control subjects were uninephrectomized F344 and Lewis rats. Twelve weeks after the operation, the rats were harvested for renal function, histological, immunohistochemical and molecular biological analyses.

Results

Rosiglitazone treatment effectively decreased urine protein excretion and preserved renal function in the CRAD rats. Administration of rosiglitazone also inhibited interstitial fibrosis and macrophage infiltration in the CRAD rat kidneys. Furthermore, rosiglitazone treatment inhibited TGF-β and NF-κB pathway activation, decreased collagen I, collagen IV, α-SMA, MCP-1, ICAM-1, TNF-α, and IL-1β expression, and increased E-cadherin expression in renal allograft tissues from the CRAD rats.

Conclusions

Rosiglitazone successfully attenuates the development of CRAD via inhibition of TGF-β signaling, the renal tubular epithelial-to-mesenchymal transition (EMT), and inflammation.

中文翻译：

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罗格列酮对大鼠慢性移植肾功能不全的保护作用。

背景

慢性移植肾功能不全（CRAD）是影响移植肾长期存活的主要疾病。罗格列酮是一种过氧化物酶体增殖物激活的受体-γ（PPAR-γ）激动剂，已被证明对某些肾脏疾病具有抗纤维化和抗炎作用。本文使用鼠模型研究了罗格列酮对CRAD的影响。

方法

CRAD组接受了经典的原位F344-Lewis肾脏移植。肾移植后治疗组用罗格列酮治疗12周。对照受试者是未切除子宫的F344和Lewis大鼠。手术十二周后，收集大鼠的肾功能，组织学，免疫组织化学和分子生物学分析。

结果

罗格列酮治疗可有效减少CRAD大鼠尿蛋白排泄并保留肾功能。罗格列酮的给药还抑制了CRAD大鼠肾脏的间质纤维化和巨噬细胞浸润。此外，罗格列酮治疗可抑制TGF-β和NF-κB途径的活化，降低胶原I，胶原IV，α-SMA，MCP-1，ICAM-1，TNF-α和IL-1β的表达，并增加E-钙粘蛋白的表达在CRAD大鼠的肾脏同种异体移植组织中

结论

罗格列酮通过抑制TGF-β信号传导，肾小管上皮向间充质转化（EMT）和炎症而成功减轻了CRAD的发展。