氨来呫诺抑制小鼠骨髓源性树突状细胞成熟的研究

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1、授予单位代码10089学号或申请号20152102中国图书分类号R744.5+1HebeiMedicalUniversity硕士学位论文学术学位氨来呫诺抑制小鼠骨髓源性树突状细胞成熟的研究研究生：刘会佳导师：宋秀娟教授专业：神经病学二级学院：河北医科大学第二医院2018年3月目录中文摘要······················································································1英文摘要·····························································

2、······························3英文缩写···························································································6研究论文氨来呫诺抑制小鼠骨髓源性树突状细胞成熟的研究前言·······························································································7材料与方法········································

3、·············································8结果·······························································································14附图······························································································17讨论···················································

4、······················································30结论·········································································································36参考文献··································································································36综述糖酵解代谢旁路与树突状细胞诱导免疫耐受的相关性··

5、··················41致谢··········································································································52个人简历··································································································53中文摘要氨来呫诺抑制小鼠骨髓源性树突状细胞成熟的研究摘要目的：树突状细胞（dendriticcell,DC）是目前已知的功能

6、最强大的抗原提呈细胞（antigenpresentingcell,APC），在免疫介导的疾病中至关重要。DC据成熟程度分为成熟树突状细胞（matureDC,mDC）和未成熟树突状细胞（immatureDC,imDC）。mDC可激活免疫应答；imDC低表达诱导免疫应答必须因子，诱发免疫耐受。因此，抑制DC成熟对于诱导免疫耐受，治疗自身免疫性疾病十分重要。ImDC发育成熟的主要代谢改变为糖酵解增强，其早期主要由TANK结合激酶1（Tank-BindingKinase1,TBK1）/核因子-κB激酶ε亚基（nuclearfactor-κBkinasesubunit-ε,IKKε）-AKT通路

7、介导。氨来呫诺（amlexanox,ALX）是新型特异性IKKε和TBK1抑制剂，可抑制糖酵解，抑制DC成熟，诱导免疫耐受。本文探究了ALX对DC成熟的抑制作用，为治疗自身免疫性疾病提供新的研究思路。方法：1.体外培养小鼠骨髓源性树突状细胞（bonemarrow-derivedcell,BMDC）将小鼠处死后取出股骨骨髓，置于含20ng/m1粒-巨噬细胞集落刺激因子（granulocyte-macrophagecolony-stimulatin