介导吸烟肺气肿th1极化notch与转录因子表达模式-th1 polarized notch and transcription factor expression pattern mediating smoking emphysema.docxVIP

独创性声明本人郑重声明，本学位论文是本人在导师指导下进行的研究工作及取得的研究成 果的总结。尽我所知，除文中已经标明引用的内容外，本论文不包含任何其他个人或 集体已经发表或撰写过的研究成果。对本文的研究做出贡献的个人和集体，均已在文 中以明确方式标明。本人完全意识到本人将承担本声明引起的一切法律后果。学位论文作者签名：日期：年月日学位论文版权使用授权书本学位论文作者完全了解学校有关保留、使用学位论文的规定，即：学校有权保 留并向国家有关部门或机构送交论文的复印件和电子版，允许论文被查阅和借阅。本 人授权华中科技大学可以将本学位论文的全部或部分内容编入有关数据库进行检索， 可以采用影印、缩印或扫描等复制手段保存和汇编本学位论文。本论文属于保密□ ，在年解密后适用本授权书。不保密□。（请在以上方框内打“√” ）学位论文作者签名：指导教师签名：日期：年月日日期：年月日Paradigm of the Expressions of Notchs and Transcription Factors that drives Th1 polarization in Cigarette Smoke Induced Pulmonary EmphysemaINTRODUCTIONChronic obstructive pulmonary disease (COPD) is characterized by airflow limitation that is progressive, not fully reversible and is associated with an abnormal inflammation response of the lungs to noxious particles and gases (1). Cigarette smoking (CS) initiates pulmonary infiltration of innate (such as macrophages, neutrophils and adaptive (dendritic cells (DCs), T and B lymphocytes, etc.) inflammatory cell, which could be the most important mechanism for the pathogenesis of COPD (2, 3).For many years, the main focus of interest has been neutrophils and macrophages (4-6). There were evidences implied that tumor necrotic factor TNF-α from macrophages might be one of the key factors in mediating the development of cigarette smoke-induced emphysema, and it was anticipated that the TNF-α accounted for approximately 70% to the development of pulmonary emphysema (6, 7). While two different trials of anti–TNF-a therapy in humans have failed to show significant improvements (8). Recent studies are also demonstrated that the Toll-like receptor (TLR4) mutation is a protective factor against pulmonary influx of inflammatory cells induced by subacute CS exposure. However, TLR4 is only minor of importance in chronic CS-induced inflammation in mice (9). Now more studies are focus on lung lymphoid follicles (LF) that known to participate in adaptive humoral and T-cell-mediated responses to antigen (10), since it has been found that the number of LF is