基于对蛋白酪氨酸磷酸酯酶1B的调节作用的姜黄素抗糖尿病的分子机制研究

Diabetes is a major health problem in China as well in the world. The incidence of diabetes is yealy inceasing in these years. The major pathology of typeⅡdiabetes is the overexpression of protein-tyrsoine phosphatese 1B（PTP1B）. Investigation the influence of drug on PTP1B is benefical to elucidate the mechanism of drug in tresting the diabetes. It has has demonstrated that curcumin played a pretectvie role in teating diabetes and diabetical nephropathy rats or mice. But there is still a long way to go for disvovering the mechanism. In this study, we will employ diabetical hepatical cell, diabetical pancreatical islets and ER stress, as well as streptozotocin and high fat diet induced diabetes mice models to study the effect of curcumin on PTP1B and downstream factors, as well as ER stress. We are also stived to discover the mechanism of curcumin in treating diabetes. These studies will lay the foundations for the research and development of diabetes medicines.

糖尿病已成为中国乃至世界医疗保健的巨大负担，而且发病率逐年升高。PTP1B的表达水平增高是Ⅱ型糖尿病的主要发病原因。探索药物对PTP1B的影响，可以深刻地揭示药物治疗糖尿病的作用机理。已有研究表明，姜黄素对糖尿病及糖尿病肾病大鼠或小鼠有一定的保护作用，但其作用机理尚未明确。本课题将利用糖尿病肝细胞模型、胰岛细胞模型和内质网应激模型，以及高脂加链脲佐菌素诱导的糖尿病模型小鼠，研究姜黄素对PTP1B及其下游因子，和内质网应激的影响，并探讨其作用机理，以期为研究和发展糖尿病药物奠定基础。

糖尿病已成为中国乃至世界医疗保健的巨大负担，而且发病率逐年升高。PTP1B 的表达水平增高是Ⅱ型糖尿病的发生和发展的主要病因。探索药物对PTP1B 的影响，可以深刻地揭示药物治疗糖尿病的作用机理。本项目研究主要利用糖尿病大小鼠模型和细胞模型，观察了姜黄素通过调节PTP1B的表达改善糖尿病大鼠的糖脂代谢的作用，发现其作用机理可能在于PTP1B 的活性，进而影响IRS和GLUT表达，调节PPARγ和C/EBPα，并促进白色脂肪的褐色化，通过调节胰岛素信号转导，影响胰岛细胞、脂肪细胞和骨骼肌细胞对葡萄糖的摄取和利用，进而改善糖尿病模型动物的糖脂代谢。通过研究，我们成功地构建了糖尿病动物模型和细胞模型，建立糖尿病药物筛选的技术平台。本研究有助于进一步深刻地揭示姜黄素的作用机理，并为探索中医药抗糖尿病的作用机理提供了有益的研究思路，同时也进一步丰富和发展中医药治疗糖尿病理论的科学内涵。