傣药雅盼抑制大鼠肾间质纤维化的分子机理研究

Renal interstitial inflammation and fibrosis are main pathological characteristics of end-stage kidney failure result in chronic kidney disease (CKD). The expression and regulation of various cytokines and abnormal accumulation of extracellular matrix (ECM) are the most important two factors in the pathogenesis of renal interstitial fibrosis. Myofibroblasts with positiveα-smooth muscle actin (α-SMA) are a group of smooth-muscle-like fibroblasts that result in expanding accumulation of extracellular matrix.in renal interstitial. Transformation growth factor beta (TGF-β) is one of the most important promoting factors of renal interstitial fibrosis. Whereas, hepatic cell growth factor (HGF) is considered as a powerful anti-fibrosis factor. In recent years, the researchers demonstrated that the traditional Chinese medicine plays a role in fighting against renal interstitial fibrosis. Three traditional Chinese medicinal materials have been extrated from 29 kind of Yunnan local medicinal materials, which have been proved to have effect on rat renal failure model in our past study. The aim of the present study is to explore the mechanism of Dai medication Yapan, which with the independent intellectual property rights in Yunnan Province and better efficacy and lowest toxicity, in renal interstitial fibrosis and inflammation. The rat renal interstitial fibrosis model with an unilateral ureters obstruction was treated with Dai medication Yapan. The expression of TGF-β, HGF andα-SMA and changing of macrophages, CD3+T cells, collagen tape Ⅰin rat renal interstitial were observed. The results of the study on cells molecule mechanism of Yapan in fighting against renal interstitial fibrosis should provide useful and important experimental evidence for its kidney protection role.

慢性肾脏病（CKD）导致的终末期肾衰竭主要病理特征为肾间质炎症和纤维化。多种细胞因子的表达调控和细胞外基质的异常积聚是肾间质纤维化中最重要的两个环节。α-平滑肌肌动 蛋白（α-SMA ）阳性的肌成纤维细胞是导致病理条件下肾间质中ECM过度沉积的主要细胞来源。转化生长因子β（TGF-β）是最重要的参与肾间质纤维化发生的促纤维化因子之一，肝细胞生长因子（HGF）被认为是强有力的抗纤维化因子。近年来发现中药有抗肾间质纤维化的作用，本项目组前期从29种云南地道药材中筛选出了3个对大鼠肾衰模型有一定疗效的药材。本研究拟在此基础上，选用其中疗效较好毒性最低的傣药雅盼治疗单侧输尿管梗阻大鼠肾间质纤维化模型，通过观察大鼠肾间质TGF-β，HGF，α-SMA表达，肾组织病理观察巨噬细胞，CD3+T细胞，I型胶原变化，探讨具有云南自主知识产权的傣药雅盼对肾脏间质纤维化和炎症细胞浸润的作用机制。

Selaginella uncinata（Desv。）Spring，傣药雅盼，又名翠云草，是一种针对炎症相关疾病的传统中药处方。在本研究中，我们研究了雅盼对大鼠模型肾纤维化的影响及其机制。通过单侧输尿管梗阻（UUO）建立大鼠肾纤维化模型。我们发现UUO大鼠肾脏的氧化应激和转化生长因子β-1（Tgf-β1），胶原-1（Col-I）和α-平滑肌肌动蛋白（α-SMA）的表达都高于对照动物中。有趣的是，雅盼水提物可以改善UUO大鼠的肾纤维化。雅盼降低了氧化应激水平和TGF-β1，Col-1和α-SMA的表达，但在用水提取物处理的UUO大鼠中有不同程度的降低。在氧化应激后，抗氧化转录因子NRF2增强由抗氧化反应元件（ARE）调节的众多基因的表达。三个基因的上游分别存在一些潜在的ARE。在这些潜在的ARE中，Col-1和α-SMA ARE各自中的一个通过功能测定确认。总之，我们的研究结果表明，雅盼水提取物通过抗氧化途径对肾纤维化具有显着疗效。雅盼对于氧化应激显著升高的广泛的病症都可能会有较好的疗效。