aurora kinase a在巨噬细胞极化过程中的调节作用word格式论文.docxVIP

英文摘要Aurora kinase A 在巨噬细胞极化过程中的调节作用及机制Role of Aurora kinase A in the Regulation of Macrophage PolarizationAbstractAurora kinase A is a serine threonnine kinase that plays an important role in mitosis and ensures correct spindle assembly in normal cells. In order to investigate the role of Aurora kinase A in the regulation of macrophage polarization, we have analyzed the expression of Aurora kinase A during the differentiation of macrophages and found an evelated expression of Aurora kinase A in M1 macrophages. This evelated expression was also found in macrophages of diseased EAE mice. In this study, we have also found that during the activation of M1 macrophages, aurora kinase inhibitor VX-680 and specific siRNA can lead to an inhibited expression of M1 specific genes through down-regulating the expression of IRF5 and inhibition of NF-κB pathway. In an autoimmune disease model, experimental autoimmune encephalitis (EAE), treatment with aurora kinase inhibitor blocked the disease development and shifted the macrophage phenotype from inflammatory M1 to anti-inflammatory M2. This study reveals a novel and critical role of Aurora kinase A in the regulation of M1 macrophages and lends great support in the clinical study of Aurora kinase A as a potential therapeutic target for inflammatory disease.Keywords: Aurora kinase A; M1 macrophage; Polarization; EAEWrittenby：Lixia Ding Supervised by：Professor Biao ZhengII目录引言 1材料与方法 111 实验材料 112 主要仪器 123 实验方法 12实验结果 201. Aurora-A 激酶在巨噬细胞中的表达情况 202. Aurora-A 激酶活性及表达下调对体外巨噬细胞极化的影响 223. Aurora-A 激酶对 M1 型巨噬细胞活化过程中信号通路的调节 254. Aurora-A 激酶抑制剂 VX-680 在小鼠 EAE 疾病模型中的作用 25讨论 31结论 3 错误！未定义书签。参考文献 34综述 38附录 47硕士期间完成的论文 48致谢 49E万植且嚣Aurora kinase A 在巨噬细胞极化过程中的调节作用及机制引 言引言Aurora 激酶Aurora 激酶的分类不功能Aurora 激酶是一类在进化过程中高度保守的丝氨酸/苏氨酸激酶，在有丝分裂 过程中，它通过参与调节中心体复制和分离、微管与着丝粒连接、染色体分离和 胞浆分裂等过程而发 挥至关重要的作用 。 自第一个 Aurora 激酶家族成员 Increase-in-ploidy (Ipl 1) 在 1993 年发现[1]，到 1998 年才确定哺乳动物体内存在三 种 Aurora 激酶，即 Aurora A、Aurora B、Aurora C[2]。人类 Aurora 激酶结构中有一 个长