B淋巴细胞调节肥胖及胰岛素抵抗的作用及机制研究

项目名称： B淋巴细胞调节肥胖及胰岛素抵抗的作用及机制研究

项目编号： No.81200586

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学二处

项目作者： 丁和远

作者单位： 复旦大学

项目金额： 23万元

中文摘要： 肥胖及胰岛素抵抗是一种慢性系统性低度炎症，与先天性免疫和获得性免疫密切相关。研究证实，巨噬细胞、T淋巴细胞、NK细胞均参与肥胖及胰岛素抵抗发病过程。但B淋巴细胞与肥胖及胰岛素抵抗相关研究甚少。有研究发现，DIO小鼠内脏脂肪组织中B淋巴细胞浸润增加。本课题组前期研究发现免疫球蛋白类别转化与肥胖及胰岛素抵抗密切相关。因此有必要进一步明确B淋巴细胞在肥胖及胰岛素抵抗中的具体作用及可能机制。 本课题采用hCD20 C57BL/6转基因小鼠和C57BL/6野生型小鼠，进行DIO造模及2H7诱导B淋巴细胞清除联合干预，通过分离原代淋巴细胞和胰岛细胞、DEXA、IPGTT、ITT、CFSE、FACS、ELISA、LUMINEX、IHC、qRT-PCR等技术，明确B淋巴细胞、B淋巴细胞清除在肥胖及胰岛素抵抗的发生、预防及治疗中的具体作用，并阐明其可能作用机制，为肥胖及胰岛素抵抗的防治提供一项崭新的思路。

中文关键词： B淋巴细胞；免疫球蛋白类别转换；肥胖；胰岛素抵抗；

英文摘要： Obesity and insulin resistance is a chronic systemic low-grade inflammation, which is closely related to innate immunity and acquired immunity. Many studies confirmed that macrophages, T lymphocytes and NK cells were involved in the pathogenesis of obesity and insulin resistance. However, little is known about the effect of B lymphocytes on obesity and insulin resistance. Studies found B lymphocyte infiltration into visceral adipose tissue increased in diet-induced-obesity mice model. Our previous data showed that the conversion of immunoglobulin class was related to obesity and insulin resistance. Therefore, it is necessary to further clarify the role of B lymphocyte in obesity and insulin resistance and its possible mechanism. hCD20 C57BL/6 transgenic mice and C57BL/6 wild-type mice are used in this project. Both high-fat diet induced obesity mice model and 2H7 induced B lymphocyte depletion are applied. To analyze the role of B lymphocytes and B lymphocytes depletion in the pathogenesis, prevention and treatment of obesity and insulin resistance and its possible mechanism, primary lymphocytes and islet cells are isolated and cultured,DEXA,IPGTT,ITT,CFSE,FACS, ELISA, LUMINEX, IHC and qRT-PCR are also applied in this project. It will provide a new idea for the prevention and treatment of obesity and insulin res

英文关键词： B lymphocyte；antibody class switch；Obesity；Insulin resistance；