幽门螺杆菌感染与2型糖尿病发生的关系及其炎症致病机制研究

项目名称： 幽门螺杆菌感染与2型糖尿病发生的关系及其炎症致病机制研究

项目编号： No.81470832

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： 吕农华

作者单位： 南昌大学

项目金额： 73万元

中文摘要： Hp感染与胃肠外疾病的关系是近年研究热点。新近研究示T2DM的Hp感染率明显升高，前瞻性研究证实Hp感染可能增加T2DM的发生风险。我们前期研究发现Hp感染在引起蒙古沙鼠胃黏膜炎症反应和炎症因子异常的同时，血清糖化血红蛋白和血红蛋白A1c水平明显升高，进一步支持Hp引起的炎症反应与T2DM的发生相关。根据T2DM的炎症致病学说，我们推测Hp感染可能是T2DM重要的炎症致病因子，其通过引起胃黏膜炎症反应和炎症因子异常，诱导胰腺和外周胰岛素敏感组织的相关细胞信号网络的紊乱，最终导致胰岛素抵抗和分泌障碍。因此，本课题拟通过建立Hp感染蒙古沙鼠动物模型，研究Hp感染引起的慢性炎症对糖代谢及胰腺和外周胰岛素敏感组织中IRS/PI3K/Akt信号通路的影响，以及根除Hp后的逆转效应，进一步深入探讨Hp感染与T2DM的关系及可能的致病机制，为T2DM的预防提供新思路，为Hp根除适应症的制定提供理论依据。

中文关键词： 幽门螺杆菌；2型糖尿病；炎症反应；细胞因子

英文摘要： The relationship between Helicobacter pylori (Hp) infection and extragastric diseases has been a hot area of research recently. Emerging data now indicate that a higher prevalence of Hp infection in people with type 2 diabetes (T2DM), and a prospective cohort study further demonstrates that Hp infection leads to an increased rate of incident diabetes. Our preliminary study revealed that Hp infection induced inflammation of gastric mucosa and the abnormal secretion of inflammatory cytokines in the Mongolian gerbils. Meanwhile, the level of glycated hemoglobin and HbA1c in Hp infected Mongolian gerbils is significantly higher than control which further support that the inflammation caused by Hp is associated with the incidence of T2DM. Accordingly, based on the inflammation pathogenic theory of T2DM, we speculate that Hp infection could probably be an important inflammatory pathogenic factor of T2DM. The possible mechanisms are the low grade inflammation caused by Hp infection and the abnormal secretion of inflammatory cytokines, which could induce disorder of intracellular signaling network of pancreas islet and peripheral insulin sensitive tissues, and eventually lead to insulin resistance and insulin secretion disability. Therefore, this project will set up Hp-infected Mongolian gerbils model, investigate the impact of Hp-infected chronic inflammation on glucose metabolism and the IRS/PI3K/Akt signaling pathways of islet and peripheral insulin sensitive tissues. Besides, we will study the reversion effect after Hp eradication to further characterize the relationship between Hp infection and T2DM and the underlying mechanisms. The resolution of this issue will provide new rational for the prevention of T2DM and the formulation of Hp eradication guideline.

英文关键词： Helicobacter pylori;type 2 diabetes;inflammation;cytokines