我们前期研究发现，高糖、TGF-β1可显著增高足细胞中细胞周期素依赖性蛋白激酶5（Cdk5）的蛋白表达水平和激酶活性，同糖尿病肾病足细胞损伤关系密切。线粒体是细胞的动力工厂，线粒体功能障碍是糖尿病肾病足细胞损伤的重要原因。我们的预实验结果发现，抑制Cdk5激酶活性，高糖导致的足细胞线粒体功能障碍也明显缓解，但具体机制尚不清楚。Drp1和PGC-1α是调节线粒体分裂及能量代谢的重要蛋白，两者的功能异常与线粒体损伤密切相关。糖尿病状态下，激酶活性异常增高的Cdk5是否可通过磷酸化调节Drp1及PGC-1α的功能，导致线粒体功能障碍并引起足细胞损伤是本课题的研究重点。我们拟利用基因转染、shRNA干扰及特异性抑制剂，通过体外、体内实验，深入探讨糖尿病肾病足细胞线粒体功能障碍的作用及机制，重点研究Cdk5在其中发挥的作用，以期为糖尿病肾病的有效防治提供新的靶点。

Our previous studies found that high glucose and TGF-β1 can significantly increase the expression and kinase activity of cyclin dependent protein kinase 5 (Cdk5) in podocytes, which was closely related to podocyte injury in diabetic nephropathy. Mitochondria are the power plants of cells. Mitochondrial dysfunction is an important cause of podocyte injury in diabetic nephropathy. Our preliminary results showed that the inhibition of Cdk5 kinase activity could relieve the mitochondrial dysfunction induced by high glucose in podocyte, but the specific mechanism is not clear. Drp1 and PGC-1α are important proteins that regulate mitochondrial division and energy metabolism, and their functional abnormalities are closely related to mitochondrial damage. Under the condition of diabetes mellitus, whether the abnormal increase of Cdk5 kinase activity can lead to mitochondrial dysfunction and podocyte injury by regulating the function of Drp1 and PGC-1α? In this study, we intend to explore the role of Cdk5 in mitochondrial dysfunction of podocyte in diabetic nephropathy by gene transfection, shRNA interference and specific inhibitors in vitro and in vivo, to provide a new target for the effective prevention and treatment of diabetic nephropathy.