DMT1在2型糖尿病骨微结构改变中的调控作用及其机制的研究

项目名称： DMT1在2型糖尿病骨微结构改变中的调控作用及其机制的研究

项目编号： No.81471094

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杨茂伟

作者单位： 中国医科大学

项目金额： 73万元

中文摘要： 随着社会进入老龄化，糖尿病等慢性疾病的发病率也逐年上升，糖尿病相关疾病越来越引起医学界的广泛关注。2型糖尿病患者骨折风险明显增高，其发病原因主要以骨微结构的改变为主，骨量并无明显变化，但具体机制尚不清楚。我们研究发现，2型糖尿病大鼠成骨细胞内出现铁离子超载现象。因此本课题从铁离子超载入手，探讨2型糖尿病大鼠的骨微结构改变的机制。该课题拟通过检测成骨细胞二价金属离子转运体（DMT1）的表达和内吞小体内铁离子的胞内释放，揭示DMT1在2型糖尿病大鼠骨组织铁超载中的调控机制。同时通过对成骨细胞氧化应激与自噬相互关系的研究，阐明成骨细胞自噬变化在2型糖尿病大鼠骨组织骨微结构改变中的主导作用。为预防2型糖尿病所致骨微结构改变及降低骨折发生风险提供新的思路和治疗靶点，具有良好的应用前景和社会价值。

中文关键词： 二价金属离子转运体；2型糖尿病；骨微结构；铁超载；自噬

英文摘要： Along with the aging problem of society, the incidence of chronic diseases such as diabetes is rising year by year, diabetes related diseases have got the attention of the medical professionals. Due to significantly increased risk of fracture in patients with type 2 diabetes, the main reason is composed of bone microstructure change, instead of bone mass, however, the specific mechanism is unclear. Our previous research revealed that the iron overload phenomenon occurred in osteoblast of type 2 diabetic rat, therefore we enlightened from the perspective of the iron overload, to explore mechanism of bone microstructure changing in type 2 diabetes rats. Our research will detect divalent metal ions transporter (DMT1) expression and endocytosis corpuscle intracellular release of iron ions in osteoblast to reveal DMT1 regulatory mechanism of iron overload in type 2 diabetic rats bone tissue. In addition, through the study of the relationship between osteoblast oxidative stress and autophagy, reveal the leading role of osteoblast autophagy in type 2 diabetic rats bone tissue microstructure changing. This research proposes a new theory in bone microstructure change caused by type 2 diabetes and provides a new therapeutic target to reduce the risk of bone fractures. So as to, it has excellent application prospect and social values.

英文关键词： Divalent metal ions transporter;Type 2 diabetes;Bone microstructure;Iron overload;autophagy