维生素D代谢异常与妊娠期糖尿病发生发展的关系：以CYP24a1和CYP27b1为靶点的机制研究

近年来，妊娠期糖尿病（gestational diabetes mellitus, GDM）的发病率持续增长，已严重影响到人口健康素质。研究发现，维生素D（vitamin D, VD）与多种代谢性疾病密切相关，为GDM的防治策略探索提供了新方向。但目前国内外关于VD与GDM的研究局限于妊娠期低VD水平是否会引发GDM。同时鉴于妊娠期VD代谢的特殊性，我们认为VD代谢异常与GDM发生发展的因果关系值得深入研究。本课题拟以VD代谢中起重要作用的CYP24a1和CYP27b1为靶点，采用妊娠期自发VD代谢异常动物模型和GDM动物模型来分别观察VD代谢异常对妊娠期糖代谢的影响和GDM状态下VD的代谢情况；并观察口服VD3和皮下包埋1,25-(OH)2-VD3对这两种动物模型的糖代谢和VD代谢的影响情况及其可能机制。旨在为确定VD代谢异常与GDM发生发展的因果关系和寻找GDM的防治途径提供新的证据。

Gestational diabetes mellitus (GDM) has now increased in prevalence worldwide and places a severe burden on health care systems. Accumulating evidences have indicated that vitamin D (VD), which is associated with many metabolic diseases, provides a new direction for the prevention and treatment of GDM. The previous studies about VD and GDM were all about the question whether VD deficiency during pregnancy would predispose individuals to GDM. However, the results were not consistent. Given the particularity of VD metabolism during gestational period, we hypothesize it is worthy to study the causal relationship between abnormal VD metabolism and the development of GDM. As CYP24a1 and CYP27b1 play important roles in VD metabolism, this program takes them as the target to study the influence of abnormal VD metabolism in gestational glycometabolism and VD Metabolism under the condition of GDM by using animal models of spontaneous abnormal VD metabolism and GDM, respectively. Furthermore, the effects and the possible mechanisms of different forms of VD on glycometabolism and VD metabolism are also studied by oral VD3 and subcutaneous embedding 1,25-(OH)2-VD3, respectively. The results of this research will provide new evidence for determining the causal relationship between abnormal VD metabolism and the development of GDM.