新近研究发现，维生素D缺乏导致胰岛素分泌和作用障碍促进糖尿病的发生及发展。糖尿病时机体内环境紊乱导致雷帕霉素靶蛋白(mTOR）过度激活并介导肾脏细胞功能紊乱，由此进一步加重维生素D缺乏。维生素D缺乏致其所诱导的DNA损伤诱导转录因子4（DDIT4）表达减少，DDIT4是mTOR重要负性调节因子，其表达减少进一步加剧mTOR信号通路异常激活及其介导的肾脏损伤，这可能是糖尿病肾病（DN）发生的重要机制。本课题首先在体外观察1,25-(OH)2VD3对肾小球上皮和系膜细胞增殖及肥大的影响并探讨其机制；然后通过构建小鼠DDIT4 SiRNA和VDR SiRNA重组腺病毒载体，感染2型糖尿病KKay小鼠，观察1,25-(OH)2VD3干预情况下对mTOR信号通路激活的影响及对肾脏的保护作用，旨在从一个新的角度探讨DN的发病机制，并为DN的防治提供新的思路。

Vitamin D deficiency has been shown to impair insulin synthesis and secretion in humans and in animal models of diabetes, playing an important role in the development of type 2 diabetes.The internal environment disorder in diabetes causes excessive activation of mTOR signal pathway, which mediates renal cell dysfunction, and further aggravates vitamin D deficiency. Vitamin D deficiency decreases the expression of DNA-damage-inducible transcript 4 (DDIT4, an important negative regulator of mTOR), which leads to further activation of mTOR signal pathway and mediates the damage of kidney. This may be an important pathogenesis mechanism of diabetic nephropathy (DN). In this study, we will first investigate the effects of 1,25-(OH)2VD3 on hyperglycemia-induced cell proliferation, hypertrophy and intracellular signaling pathway in cultured mouse glomerular epithelial cell and mesangial cell. Then we will verify the protective effects of 1,25-(OH)2VD3 on early DN and detect the activation level of mTOR pathway in type 2 diabetes KKay mice which are infected with a recombinant adenovirus vector encoding mouse DDIT4 SiRNA or VDR SiRNA. This project aims to explore the pathogenesis of DN from a new perspective and provide new ideas on the prevention and treatment of DN.