肾小管损伤是糖尿病肾病（DN）发生发展的基础，大量活性氧簇（ROS）介导的肾小管上皮细胞间充质转分化（EMT）是DN肾小管损伤的关键环节。电子转移黄素蛋白β亚单位（ETFβ）可通过影响NADPH氧化酶和脂肪酸氧化途径参与ROS的产生。我们前期在差异蛋白质组学研究中发现自发性2型DN大鼠模型的ETFβ发生突变。因此，我们推测DN时ETFβ 异常是肾脏产生过量ROS，进而引起DN肾小管上皮细胞EMT的重要机制。针对DN的核心病机"气阴两虚夹瘀"，课题组研发了以益气养阴活血通络为治则的中药复方糖肾方，临床研究发现该药对DN有确切疗效同時基础实验证明其能显著改善肾小管病理损害及纤维化的作用。本研究拟采用基因转染、RNA干扰等技术，运用糖肾方从体内、外两方面验证ETFβ通过产生大量ROS参与DN肾小管上皮细胞 EMT发生的科学假说，同时阐明益气养阴活血通络法治疗DN抗肾小管间质纤维化的作用机制。

Renal tubular injury is critical for the pathogenesis of diabetic nephropathy(DN). Epithelial to mesenchymal transition (EMT) mediated by ROS is considered to be an important mechanism of tubular injury in DN. Nevertheless, the origin of ROS in the kidney is unclear yet. In the previous study, we found that electron-transferring flavoprotein β subunit (ETFβ) mutated in OLETF rats by proteomics and over expression of ETFβ could reduce mRNA expression of NOX4, which lead to the production of ROS in the kidney. Consequently, we speculate that ROS originates from ETFβ mutation in the renal tubular may be important to EMT of diabetic nephropathy. The deficiency of QI and YIN with stasis is the main interpretation of DN. Tangshen Formula developed by Yi-qi Yang-yin and Huo-xue Tong-luo principle，which has the definite curative effect and alleviates pathological lesion and fibrosis in the renal tubular. In this study, we will justify the hypothesis that ETF participant in tubular EMT via production of excess ROS by gene transfection and siRNA both in vivo and in vitro experiments. Furthermore, the influence of Tangshen Formula on the biomarkers of EMT, ROS production, and the expression and activity of ETFβ is also to be analyzed. The study will reveal the mechanism of Tangshen Formula on alleviating pathological lesion and fibrosis in the renal tubular, and replenish the connotation of Yi-qi Yang-yin and Huo-xue Tong-luo principle.