評估甘胺酸螯合鐵減緩腎間質纖維化之功效

慢性腎衰竭的病人是指腎功能逐漸衰退且無法逆轉的現象，其中腎間質纖維就是一個腎臟疾病產生的重要現象。主要是腎臟損傷時腎絲球造成大量發炎細胞活化，進而產生活性氧分子及誘導纖維化路徑。甘胺酸敖合鐵(ferrochel)是指兩個甘胺酸與一個亞鐵離子螯合鍵結而成，本身具有高度生物利用率與生理作用，然而與腎臟纖維化之相關研究及分子機轉仍然未知。本研究計畫利用單側輸尿管阻塞 (Unilateral ureteral obstruction, UUO)的小鼠腎臟纖維化動物模式證實甘胺酸敖合鐵抑制小鼠腎間質纖維化，不會產生鐵離子堆積，同時也抑制UUO誘導膠原纖維產生、纖維化蛋白(-SMA、collagen I)和間質蛋白(vimentin)的蛋白表現，此外也觀察到甘胺酸敖合鐵減少尿液中肌酸酐(creatinine)和尿素氮(BUN)表現。接下來利用乙型轉化生長因子(Transforming Growth Factor-beta1，TGF-1)誘導正常腎小管HK2細胞移動模式證實甘胺酸敖合鐵不會對腎小管HK2細胞產生細胞毒性，但是甘胺酸敖合鐵會減少TGF-1誘導細胞移動作用及抑制纖維化蛋白(α-SMA、collagen I)和間質蛋白(vimentin)的蛋白表現。總之，本研究提供甘胺酸敖合鐵抗腎臟纖維化之之研究，未來甘胺酸敖合鐵也許可以成為一個有效的策略來改善腎臟纖維化以及副作用所帶來的影響。同時也證實減緩腎損傷與抗腎臟纖維化保護機制功能的小分子藥物，期望研究結果能有所助益。

Chronic renal disease refers to the progressive and irreversible decline in human kidney function. Renal interstitial fibrosis is a critical role in kidney disease. When kidney injury, it’s leads to the activation of inflammatory cells in the glomerulus, resulting in the production of reactive oxygen species and the induction of fibrotic pathways. Ferrochel, a complex formed by two glycine molecules and one ferrous ion, and possesses high bioavailability and physiological effects. However, anti-fibrotic effect and molecular mechanisms of ferrochel in renal interstitial fibrosis is remain unclear. This study aims to investigate the effects of ferrochel on renal fibrosis using a unilateral ureteral obstruction (UUO) mouse and in vitro cell line model. Our results suggest that ferrochel inhibits renal interstitial fibrosis in mice without accumulated the iron ion in kidney tissues. Ferrochel also inhibits collagen fiber accumulation and the expression of fibrotic proteins (α-SMA, collagen I) and mesenchymal proteins (vimentin) induced by UUO mice model. Furthermore, ferrochel decreased expression of creatinine and nitrogen (BUN) in urine of UUO mice. In vitro cell model, using human kidney tubular epithelial (HK2) cells found that ferrochel does not induce cytotoxicity, but decreased TGF-β1 (Transforming Growth Factor-β1)-induced cell migration and the expression of fibrotic proteins (α-SMA, collagen I) and mesenchymal proteins (vimentin). Taken together, the present study reveals that ferrochel may be an effectively strategy for improving the problems of side-effect and renal fibrosis. We also demonstrated that the ferrochel alleviate kidney damage and protecting against renal fibrosis, with the hope that the research results will be beneficial.