肾小球足细胞损伤加重肾脏疾病进展至终末期，是世界性难治病症之一，因此，加强足细胞损伤关键病理环节与有效安全药物发现研究甚为重要。课题组前期已证实高果糖可诱导动物产生代谢综合征与蛋白尿，呈现腺苷酸激活蛋白激酶（AMPK）变化所介导的糖脂代谢失衡和线粒体功能受损为特征的足细胞损伤。桑色素可逆转高果糖诱导足细胞AMP脱氨酶（AMPD）2表达异常保护线粒体功能并减轻肾损伤，但其分子机制尚不十分清楚。本项目拟在上述动物和足细胞模型及AMPD2-/-敲除小鼠上进一步探寻AMPD2低表达促进AMPK变化所介导的代谢重编程，进而改变线粒体功能等足细胞损伤的关键病理环节；重点研究桑色素调控AMPD2改善代谢重编程，重构代谢稳态恢复线粒体功能，减轻足细胞损伤新的药理学机制，从中发现新的潜在药物靶标，对防治代谢综合征肾小球足细胞损伤具有重要的科学意义。

Glomerular podocyte injury, as one of the world’s refractory diseases accelerates the development of kidney disease to end-stage failure. Therefore, it is an urgent task to elucidate the pathological links of podocyte injury, as well as developing effective and safe drugs. We have demonstrated that high fructose induced metabolic syndrome and proteinuria in experimental rodents, exhibiting podocyte dysfunction characterized by the disturbance of AMPK-mediated carbohydrate and lipid metabolism, as well as functional changes of mitochondria. We have also proved that morin alleviated mitochondria injury and kidney dysfunction by restoring AMPD2 dysregulation induced by fructose in podocyte. However, the detailed mechanism needs to be further elucidated. Based on the above animal and podocyte models, as well as AMPD2-/- mice, this project aims to further investigate the crucial pathological mechanism of AMPD2 reduction to induce AMPK-mediated metabolism reprogramming, which will alter mitochondria function in podocyte under high fructose. The key of this project will focus on the new regulatory mechanism of morin on AMPD2 to reconstruct metabolism reprogramming, and improve mitochondria function, which will reduce podocyte injury. This innovative work will elucidate the protective mechanism of morin against glomerular podocyte injury, discover new potential drug targets, and be of great scientific significance for the prevention and treatment of glomerular podocyte injury in metabolic syndrome.