基于Nrf2抗氧化通路探索三黄消炎方治疗糖尿病足的作用机制研究

糖尿病足(DF)是糖尿病严重并发症之一，中医认为，湿郁筋损是其主要发病机制，遂化湿消炎（消除炎症）为其主要治疗手段。本院经典方剂三黄消炎方用于临床治疗DF有数十载取得显著疗效，作用机制尚不明确。有文献报道，抗氧化蛋白Nrf2在DF中抑制炎症加速伤口愈合。预实验中，DF模型中给予三黄消炎方处理可减轻炎症程度，伴随着Nrf2蛋白表达的上调以及其上游蛋白AMPK和下游的HMGB1蛋白表达的下调。遂推测：该通路是三黄消炎方治疗DF的重要作用机制。本项目拟在DF动物和细胞模型上，并结合运用遗传学工具（Nrf2基因敲除小鼠）建立DF模型，探讨三黄消炎方是否通过AMPK/Nrf2/HMGB1发挥治疗作用，进一步寻求治疗DF的新药物和其靶点。

Diabetic foot (DF) is one of the serious complications of diabetes. TCM believes that dampness depression and tendons damage are the main pathogenesis of diabetic foot, and the main treatment method is to eliminate inflammation. The traditional prescription Sanhuang Xiaoyan prescription has been used in clinical treatment of DF for several decades, and the mechanism of action is not clear. It is reported that Nrf2 can inhibit inflammation and accelerate wound healing in DF. In the pre-experiment, the treatment of Sanhuang Xiaoyan prescription in DF model can reduce the inflammation degree, along with the up-regulation of expression of Nrf2, AMPK and the down-regulation of HMGB. It is suggested that this pathway is an important mechanism of treating DF by Sanhuang Xiaoyan prescription. In this project, we intend to use DF animal and cell models to explore whether Sanhuang Xiaoyan prescription can play a therapeutic role through AMPK/Nrf2/HMGB1, and further seek new drugs and targets for DF treatment.