TGF-β1/HGF的失衡在糖尿病肾病（DN）发生发展具有重要作用，硫酸酯酶1（Sulf1）可通过影响HSPG的硫酸化状态调控TGF-β1/HGF信号的平衡。前期研究发现：Sulf1在DN患者肾活检样本及动物模型表达显著升高，但其在DN中的作用尚不明确；治疗DN疗效确切的柴黄益肾颗粒能抑制DN大鼠Sulf1表达。基于此发现，本研究拟利用慢病毒转染、qPCR、Western blot及流式细胞等技术，结合动物及细胞实验，分析Sulf1介导的TGF-β1/HGF失衡与DN病变的相关性，揭示其在DN中的作用及柴黄益肾颗粒的调控机制，进而利用分子对接与虚拟筛选技术，筛选对Sulf1的柴黄益肾颗粒单体成分，并通过Luciferase reporter技术验证其对TGF-β1信号的作用。本研究对于DN药物新靶标的发现及柴黄益肾颗粒治疗DN分子机制及生物学内涵的阐释，具有重要意义。

TGF-β1/HGF imbalance plays an crucial role in the pathogenesis of diabetic nephropathy(DN). Sulf1 can regulate the balance of TGF-β1/HGF signaling by affecting the sulphated state of HSPG. Our previous studies has firstly revealed the increased expression of Sulf1 in renal biopsys from DN patients and kidney from DN rats. Changhuang-Yishen Granule(CHYS) could reverse the upregulation of renal Sulf1 expression in DN.However, the role of Sulf1 in DN remains to be clarified. In this study, we try to investigate the role of Sulf1-mediated TGF-β1/HGF imbalance in DN, and to explore the intervention mechanism of CHYS by lentivirus transfection, qPCR, Western blot and flow cytometry techniques, combined with animal and cell experiments. Futhermore, molecular docking and virtual screening will be used to screen components of CHYS with high affinity to Sulf1, and their effect on TGF-β1 signaling was verified by the luciferase reporter technique.The research will exhibit important significance in exploring the new target of drugs in DN, and revealing the molecular mechanism and biological connotation of CHYS in treating DN.