肥胖相关炎症诱导的M1型巨噬细胞分化调控肥胖型哮喘临床表型机制研究

Obesity-asthma phenotype has been the hot topic in recent years and is intensively concerned by asthma researchers worldwide. Macrophage as one of the key components in innate immunity, plays the central role in host immune defense, characterized by plasticity and polarization. Obesity-associated inflammation in imbalance of leptin/adiponectin in adipose tissue induces macrophage phenotypetransformation from M2 to M1, which may be the potential mechanism of cellular immunology in obesity-asthma phenotype. With the guidance of "Obesity-associated inflammation inducingmacrophage phenotype transformation", this proposed project will apply clinical trial method, gene-microarray bioinformatics, flow cytometry, cell culture, induced-sputum, real-time PCR, Western blot, to explore macrophage phenotype and function in obesity-asthma phenotype in vivo and vitro, and to clarify neutrophil inflammation, corticosteroid resistance, and susceptibility of respiratory virus infection (asthma exacerbation) in obesity-asthma phenotype. Furthermore, it could screen the drug target in corticosteroid resistance by using gene-microarray bioinformatics and corticosteroid resistance-associated inflammation pathway, which could provide the scientific evidence contributing improvements in total control of obesity-asthma phenotype.

肥胖型哮喘是近年关注的热点。巨噬细胞是固有免疫的关键成分，在炎症和宿主免疫防御中起核心作用，具有可塑性与极化特征。肥胖脂肪组织以瘦素（leptin）/脂联素（adiponectin）失衡为主的炎症微环境诱导巨噬细胞M2型向前炎性M1型转化，可能是肥胖型哮喘临床表型的细胞免疫学基础。本课题以"肥胖相关炎症诱导的巨噬细胞表型转化"为主导思路，采用临床对照试验，利用基因芯片-生物信息分析、流式细胞技术、细胞培养、诱导痰、荧光定量PCR、Western blot等方法，从体内外、多层次，分析肥胖型哮喘巨噬细胞表型及功能，并探索与此相关肥胖型哮喘临床表型特征，为阐释肥胖型哮喘中性粒细胞气道炎症、激素抵抗及呼吸道病毒易感性（所致哮喘急性发作）提供科学证据。而且，通过基因芯片-生物信息分析及体外激素抵抗炎症通路研究，可为肥胖型哮喘筛选预防或治疗激素抵抗的药物靶点，为改善肥胖型哮喘的整体控制提供科学依据。

肥胖型哮喘是近年关注的热点。巨噬细胞是固有免疫的关键成分，在炎症和宿主免疫防御中起核心作用，具有可塑性与极化特征。肥胖脂肪组织以瘦素（leptin）/脂联素.（adiponectin）失衡为主的炎症微环境诱导巨噬细胞M2 型向前炎性M1 型转化，可能是肥胖型哮喘临床表型的细胞免疫学基础。本课题以"肥胖相关炎症诱导的巨噬细胞表型转化"为主导思路，采用临床对照试验，利用基因芯片-生物信息分析、流式细胞技术、细胞培养、诱导痰、荧光定量PCR、Western blot 等方法，从体内外、多层次，分析肥胖型哮喘巨噬细胞表型及功能，并探索与此相关肥胖型哮喘临床表型特征，为阐释肥胖型哮喘中性粒细胞气道炎症、激素抵抗及呼吸道病毒易感性（所致哮喘急性发作）提供科学证据。而且，通过基因芯片-生物信息分析及体外激素抵抗炎症通路研究，可为肥胖型哮喘筛选预防或治疗激素抵抗的药物靶点，为改善肥胖型哮喘的整体控制提供科学依据。