First Clinical Medical College of Nanjing Medical University, Nanjing 210029, P. R. China.
Biol Pharm Bull. 2011;34(8):1219-26. doi: 10.1248/bpb.34.1219.
Renal interstitial fibrosis is a common outcome of a variety of chronic renal diseases. Here we evaluated the therapeutic efficacy of rhein on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO) and investigated the potential mechanisms. Mice underwent UUO, followed by orally administrated rhein (150 mg/kg/d) or control vehicle. Renal interstitial injury and the degree of fibrosis were evaluated by pathological staining and Western blot. The possible mechanisms were studied by Western blot, indirect immune-fluorescence and enzyme-linked immunosorbent assay. Our results showed that rhein therapy markedly ameliorated renal interstitial fibrotic lesions, reduced α-smooth muscle actin (α-SMA) expression, attenuated deposition of fibronectin (FN). Rhein also suppressed transforming growth factor-β1 (TGF-β1) and its type I receptor expression in obstructed kidneys. In vitro, rhein abolished the α-SMA and fibronectin expression of rat kidney interstitial fibroblasts cells (NRK-49F) induced by TGF-β1. These observations strongly suggest that rhein is a potent inhibitor of renal interstitial fibrosis, and its therapeutic mechanism is, at least in part, blocking interstitial fibroblasts cells activation.
肾间质纤维化是多种慢性肾脏疾病的共同结局。在这里，我们评估了大黄酸对单侧输尿管梗阻（UUO）诱导的肾间质纤维化的治疗效果，并研究了其潜在机制。小鼠接受 UUO 手术，随后给予大黄酸（150mg/kg/d）或对照载体口服治疗。通过病理染色和 Western blot 评估肾间质损伤和纤维化程度。通过 Western blot、间接免疫荧光和酶联免疫吸附试验研究可能的机制。我们的结果表明，大黄酸治疗明显改善了肾间质纤维化病变，减少了α-平滑肌肌动蛋白（α-SMA）的表达，减轻了纤维连接蛋白（FN）的沉积。大黄酸还抑制了梗阻肾脏中转化生长因子-β1（TGF-β1）及其 I 型受体的表达。在体外，大黄酸消除了 TGF-β1诱导的大鼠肾间质成纤维细胞（NRK-49F）中α-SMA 和纤维连接蛋白的表达。这些观察结果强烈表明，大黄酸是一种有效的肾间质纤维化抑制剂，其治疗机制至少部分是通过阻断间质成纤维细胞的激活。
