Osteopontin介导Bim调控B细胞自身功能参与实验性自身免疫性重症肌无力发生、发展的实验研究

项目名称： Osteopontin介导Bim调控B细胞自身功能参与实验性自身免疫性重症肌无力发生、发展的实验研究

项目编号： No.81471227

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： 穆莉莉

作者单位： 哈尔滨医科大学

项目金额： 70万元

中文摘要： 重症肌无力（MG）是B细胞介导T细胞依赖的自身免疫性疾病，以往对其发病机制研究过分强调了T细胞对B细胞的调节，忽视了B细胞自身调节作用。我们前期实验证实B细胞自我调控在MG/EAMG中的作用尤为重要，并提出Osteopontin-Bim-B细胞免疫调节轴这一新概念，即当B细胞受到OPN活化后导致其内促凋亡基因Bim表达下降，自身反应性B细胞清除减少，大量带有针对自身神经肌肉接头处乙酰胆碱受体抗体的B细胞在体内蓄积，分泌抗体，促使MG/EAMG发生。本课题以MG/EAMG为研究对象，利用Bim基因敲除鼠、OPN体内预防性治疗等平台旨在研究在MG/EAMG中OPN、Bim如何参与疾病过程；阐明Bim对B细胞增殖、凋亡、抗体分泌的影响及具体途径；确定影响Bim作用的相关因素，探讨Opn-Bim-B细胞免疫调节轴具体机制。这些问题解决不仅丰富MG/EAMG发病机制内容，对临床靶点治疗MG意义重大。

中文关键词： 重症肌无力；促凋亡蛋白Bim；B细胞；T细胞；骨桥蛋白

英文摘要： Experimental Autoimmune Myasthenia Gravis is(EAMG）an animal model of myasthenia gravis （MG）,is a rare organ-specific autoimmune disease targeting the autoantigen nicotinic acetylcholine receptor (AChR). It has demonstrated that the major reason caused the disease is the antibody secreted by the activated B cell. Some papers showed that the prolonged survival of B cell, which was related with the expression of pro-apoptosis gene Bim, played very important role in autoimmune disease.The results in our preliminary experiment showed that the expression of Bim is reduced after stimulation in B cells. This reflect that there should be any relationship between Bim and the disease EAMG. Also, other's paper showed that Osteopontin could regulate the pro-apoptosis role of Bim and in our experiment we found that after stimulated by osteopontin, the expression of Bim is decreased in B cells. All of these indicated that Bim and Osteopontin maybe could affact the survival of B cell during the development of EAMG. Base on thess and our preliminary experiment results, our research aim to find out the gaps in the regulation among Osteopontin-Bim-B cell in immunal system and in the development of EAMG, that can enrich the theoretical content of how MG/EAMG occurrence and we can provide a new theretical basis and experimental foundation for MG clinical treatment.

英文关键词： Experimental Autoimmune Myasthenia Gravis;Bim;B cell;T cell;Osteopontin