肺部菌群通过LPS调控肺巨噬细胞MMP表达介导COPD肺气肿发生的作用及机制研究

慢性阻塞性肺疾病（COPD）是严重威胁人类健康的慢性疾病，而肺气肿既是COPD重要的病理表现，也是反映疾病进展及预后的重要标志。多项观察性研究发现COPD患者肺部菌群的改变与肺气肿的发生有关，但因果关系及具体机制尚不明确。我们前期研究发现：肺部菌群的改变先于肺气肿发生，且与肺部基质金属蛋白酶9、12（MMP-9、MMP-12）升高有关；通过生物信息学发现COPD肺部菌群中LPS的合成代谢显著增强。进而提出科学假说：肺部菌群在COPD病理过程中通过增加LPS的合成代谢，诱导肺泡巨噬细胞分泌MMP-12及MMP-9，从而介导肺气肿的发生。本研究拟在前期研究的基础上进一步明确肺部菌群与肺气肿及MMP炎症的因果关系；阐明肺部菌群是否通过LPS调控肺泡巨噬细胞的MMP炎症反应及相关信号分子通路；同时使用健康小鼠的肺部菌群提取物进行气道滴注，探究肺部菌群移植在COPD或肺气肿治疗或预防中的作用。

Chronic obstructive pulmonary disease (COPD) is a chronic disease that severely threaten human health. Emphysema is an important pathological manifestation and also a key feature reflecting disease progress and prognosis. Several observational studies found that alteration of lung microbiota in COPD patients is related to occurrence of emphysema, however, the causal relation and mechanism is still unclear. Our preliminary study found that the shift of lung microbiota is prior to occurrence of emphysema and is related to increase of matrix metalloproteinase (MMP)-9 and MMP-12 in lung; found that anabolism pathway of lipopolysaccharide (LPS) is obviously increased in COPD via bioinformatics analysis. This current study aimed to be on the basis of the preliminary study further to determine the causal relationship between lung microbiota and emphysema and MMP inflammation; to elucidate whether lung microbiota regulated MMP inflammation lung macrophage and the related signal molecular pathway; to explore the role of respiratory microbiota transplantation in therapy and prevention of emphysema through airway instillation of pulmonary microbiota exact from healthy mice.