高剂量维生素D拮抗镉负荷下糖尿病肾损伤的实验研究

目前，维生素D的每日推荐摄入量是以满足健康人群最基本需要为基准的。此剂量与其中毒剂量之间有很大的空间。国内外不同的学会都在谨慎地提高维生素D的每日推荐摄入量。因此，高剂量维生素D的生物效应值得研究。.研究发现低剂量镉负荷显著增加糖尿病肾脏并发症。近年来，我国糖尿病患病率升高、镉污染普遍。肾小管损伤是镉污染与糖尿病肾病的共同靶标。本项目探索高剂量维生素D拮抗镉负荷下糖尿病肾损伤的效果及其机制。最新研究发现高剂量维生素D以维生素D受体非依赖方式直接与SREBP裂解激活蛋白 (SCAP)结合，导致后者裂解从而调节肾小管上皮细胞。这一直接作用的证实不仅为维生素D用于镉负荷下的糖尿病防治提供理论基础，而且是在维生素D理论上的一个重要突破，丰富维生素D的理论，促进营养学科的发展。本项目为镉负荷下糖尿病肾病防治提供一个新思路，同时，还可以为下次维生素D每日推荐摄入量的修订提供重要数据。

At present, Dietary reference intakes for vitamin D is based on this dose can meet the needs of healthy people. However, as more non-classic effects of vitamin D have been found, the effects of high dose vitamin D are an urgent research field. The prevalence of diabetes in China has increased significantly in recent years. Cadmium pollution is also very common at same time. Previous studies have found that low-level cadmium body burden significantly increased the prevalence of diabetic nephropathy. Renal tubular injury is the same target of cadmium pollution and diabetic nephropathy. Based on the study of the biological effects of high dose vitamin D, this proposal explored the effect and mechanism of high dose vitamin D on the combined renal dysfunction of diabetes and low-level cadmium body burden. It is reported that 25-hydroxyvitamin D (25OHD) impairs Sterol regulatory element binding proteins (SREBP) activation independently of the vitamin D receptor. It is a previously unrecognized molecular mechanism of vitamin D that might contribute to protecting renal tubular epithelial cells and islet beta-cells. VDR-independent effect of vitamin D will enrich the theory of vitamin D and promote the development of nutrition. This proposal can not only provide a new idea for the prevention and treatment of diabetes under the condition of cadmium load, but also there will be a breakthrough in vitamin D study once the direct action of 25-hydroxyvitamin D is confirmed. Therefore, this proposal has both theoretical and practical value.