Department of Nephrology and Rheumatology, Kinki University Faculty of Medicine, Osaka, Japan.
Nephron Exp Nephrol. 2011;118(3):e69-78. doi: 10.1159/000322409. Epub 2011 Jan 13.
Retinoic acids, a group of natural and synthetic vitamin A derivatives, have potent anti-proliferative, anti-inflammatory and anti-fibrotic properties. We investigated the therapeutic effect of all-trans-retinoic acid (ATRA) on unilateral ureteral obstruction (UUO) model mice.
First, to evaluate the prophylactic effect, we administered 0.5 mg of ATRA for 3 days before UUO (UUO ATRA). Then, to evaluate the therapeutic effects, we administered 0.5 mg of ATRA 3 days after UUO (Day 3 ATRA). We compared the histological changes and immunostaining of macrophages, α-smooth muscle actin (α-SMA) and collagen I, and mRNA expression of monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-β(1) and TGF-β R-II by RT-PCR 7 days after UUO.
In the UUO ATRA and Day 3 ATRA groups, we observed a significant improvement in histological and immunological findings, including macrophage infiltration and improved expression of MCP-1, TGF-β(1), α-SMA and collagen I compared with the UUO Day 7 group.
ATRA treatment is not only an effective prophylactic strategy, but also a therapeutic strategy for the treatment of progressive renal fibrosis in diseased kidneys.
维甲酸是一组天然和合成的维生素 A 衍生物,具有很强的抗增殖、抗炎和抗纤维化作用。我们研究了全反式维甲酸(ATRA)对单侧输尿管梗阻(UUO)模型小鼠的治疗作用。
首先,为了评估预防作用,我们在 UUO 前 3 天给予 0.5mg ATRA(UUO ATRA)。然后,为了评估治疗效果,我们在 UUO 后 3 天给予 0.5mg ATRA(第 3 天 ATRA)。我们比较了 UUO 后 7 天组织学变化和巨噬细胞、α-平滑肌肌动蛋白(α-SMA)和胶原 I 的免疫染色,以及单核细胞趋化蛋白-1(MCP-1)、转化生长因子(TGF)-β(1)和 TGF-β R-II 的 mRNA 表达通过 RT-PCR。
在 UUO ATRA 和第 3 天 ATRA 组中,与 UUO 第 7 天组相比,我们观察到组织学和免疫学发现有显著改善,包括巨噬细胞浸润和 MCP-1、TGF-β(1)、α-SMA 和胶原 I 的表达改善。
ATRA 治疗不仅是一种有效的预防策略,也是治疗病变肾脏进行性肾纤维化的治疗策略。