过敏毒素C5a在慢性阻塞性肺病气道重构中的作用及机制

Chronic obstructive pulmonary disease (COPD) is a chronic airway inflammation caused by irreversible airway remodelling as the main pathophysiological characteristics of the disease. Inhibition of airway chronic inflammation for improvement of airway remodelling, delay the progression is of great significance. Our initial clinical studies found that C5a allergy toxin may participate in chronic airway inflammation, but the specific mechanism of the present study is less understood. This study put forward the hypothesis that inhibition of C5a receptors can reduce airway smooth muscle cell generation MCP - 1, reduce CD45 + / CD34 + cells (Fibrocyte) infiltration, delay airway remodelling. To verify the above hypothesis, COPD mice model was established, by venous allergy toxin C5aR mAb to drug knockout C5aR understand C5a plays the role of chronic airway inflammation in mice, and inhibit C5a receptors to suppress chronic airway inflammation, improve the significance of airway remodeling, provide theoretical basis for further mechanism research, looking for new targets for the treatment of COPD.

慢性阻塞性肺疾病（COPD）是一种以慢性气道炎症引起的不可逆的气道重构为主要病理生理特征的疾病。抑制气道慢性炎症对于改善气道重构、延缓病情进展具有重要意义。我们前期临床研究发现过敏毒素C5a可能参与慢性气道炎症，但具体机制目前研究尚少。本研究提出假说：抑制C5a受体可以减少气道平滑肌细胞生成MCP-1，减少CD45+/CD34+纤维细胞（Fibrocyte）浸润增加，延缓气道重构。为验证上述假说，拟建立COPD小鼠模型，通过静脉给予过敏毒素C5aR mAb对C5aR进行药物敲除，了解C5a在小鼠慢性气道炎症中发挥的作用，以及抑制C5a受体对于抑制慢性气道炎症、改善气道重构的意义，为进一步机制研究提供理论依据，为COPD的治疗寻找新的靶点。