基于LncRNA-Gm6135/miR203介导的TLR4通路探究“从风论治”治疗糖尿病肾脏病的机制研究

免疫炎症反应在糖尿病肾脏病（DKD）的发生发展中起着重要作用。LncRNA-Gm6135/miR-203轴是肾小球系膜细胞TLR4的重要激活途径，可以激发多种炎症因子释放，导致系膜细胞增生、肾小球硬化、纤维化。本团队前期研究显示“从风论治”代表方—益气祛风方与TLR4通路具有较强的关联性。据此提出“从风论治通过LncRNA-Gm6135/miR-203轴抑制TLR4通路，减少系膜细胞的增生”的假说。课题以TLR4通路为切入点，以动物整体实验与细胞实验相结合的方式，采用miR-203及TLR4相应的抑制剂和激活剂，探究益气祛风方及其拆分方基于LncRNA-Gm6135/miR-203轴对TLR4及系膜细胞增生的调控作用。在组方-血清中药物成分-炎症指标-炎症通路-网络药理-实验数据的关联性分析基础上揭示益气祛风方的作用机制及特色，阐明“从风论治”的科学内涵，为中医药治疗DKD提供新思路。

Immune inflammatory response plays an important role in the development of diabetic renal disease (DKD).LncRNAGm6135/ mir-203 axis is an important activation pathway of glomerular mesangial cell TLR4, which can stimulate the release of various inflammatory factors, leading to mesangial cell proliferation, glomerulosclerosis, and fibrosis. Our team's previous research shows that the representative prescription of "wind-based treatment" --Yi Qi Qu Feng formula has a strong correlation with the TLR4 pathway. Based on this, the hypothesis that "Yi Qi Qu Feng formula regulates the TLR4 pathway through lncRNA-gm6135 / mir-203 axis to reduce mesangial cell proliferation" was proposed. This study will take the TLR4 pathway as the entry point, combine the animal experiment with the cell experiment, and adopt the corresponding inhibitors and activators of miR203 and TLR4 to explore the regulatory effect of Yi Qi Qu Feng formula and its splitters on the proliferation of mesangial cells through the lncRNA-gm6135 / mir-203 axis. Based on the correlation analysis of the prescription - serum drug components - inflammatory indicators - inflammatory pathway - network pharmacology - experimental data, the mechanism and characteristics of Yi Qi Qu Feng formula were revealed, the scientific connotation of "wind-based treatment" was clarified, and a new therapeutic approach was provided for the treatment of DKD by traditional Chinese medicine.