糖尿病肾病（DKD）是糖尿病最常见的微血管并发症，研究有效防治DKD的药物对于降低糖尿病患者死亡率有重要意义。Silybin可降低DKD患者尿蛋白含量，但作用机制不明。我们发现，Silybin可改善肥胖小鼠肾脏脂质代谢异常，并刺激线粒体生物合成。进一步研究发现：在DKD大鼠肾小管组织中，GHSR-1a、AMPK、Parkin表达被抑制，Silybin治疗后表达均增加，线粒体自噬与合成被激活。据此，我们提出假说：Silybin作用于肾小管GHSR-1a受体，激活AMPK/Parkin通路，启动受损线粒体自噬清除、促进生物合成，维持数量与质量稳态，从而恢复能量代谢、改善肾脏功能。本研究拟应用DKD动物模型、细胞损伤模型，结合RNA干扰、质粒载体表达、Tag-lite检测、免疫荧光、透射电镜等技术，以线粒体稳态调控为新切入点，探讨Silybin肾脏活性的产生机制，为应用于临床防治DKD奠定基础。

Diabetic nephropathy (DKD) is the most common microvascular complications of diabetes, the study of effective prevention and treatment of DKD drugs for reducing the mortality of diabetic patients is of great significance. Silybin can reduce urinary protein in diabetic patients, but the mechanism of action is unknown. We found that Silybin can improve kidney dyslipidemia in obese mice and stimulate mitochondrial biosynthesis. Further study found that: in the renal tubular epithelial cells of DKD rats, the expression of GHSR-1a, AMPK and Parkin were inhibited, Silybin treatment increased expression, mitochondrial autophagy and synthesis was activated. Accordingly, we propose the hypothesis that Silybin acts on the tubular GHSR-1a receptor, activates the AMPK / Parkin pathway, initiates the autophagy clearance of damaged mitochondrion, promotes biosynthesis, maintains the homeostasis of quantity and quality, thus restoring energy metabolism and improving renal function. In this study, we will use DKD animal models, cell injury model, combined with RNA interference, plasmid expression vector, Tag-lite detection, immunofluorescence, transmission electron microscopy and other techniques, taking mitochondrial homeostasis regulation as a new entry point to explore the mechanism of Silybin’s renal activity, which could lay the foundation for the clinical prevention and treatment of DKD.