肺泡上皮细胞损伤、坏死和修复异常等改变与COPD发病密切相关，有效修复损伤肺泡上皮对治疗COPD、改善预后有决定性影响。外源性MSCs可分化为肺泡上皮细胞，为COPD治疗提供了新途径，但其低分化率严重阻碍了MSCs的应用。Wnt/β-catenin信号通路可能在MSCs上皮分化中起关键调节作用，干预该通路可能从根本上提高MSCs对COPD的治疗。本研究首先体外MSCs与COPD肺泡上皮细胞共培养，观察激活和抑制Wnt/β-catenin信号通路对MSCs增殖、侵袭及肺泡上皮分化的影响；然后复制大鼠COPD模型，以激活Wnt/β-catenin信号通路为切入点，给予Wnt3a基因转染的MSCs，观察该信号通路激活对MSCs向肺泡上皮细胞分化，及对肺泡上皮结构与功能的影响，为阐明该信号通路对MSCs在COPD肺泡上皮修复和结构重建中的调节作用提供新依据，为COPD的细胞治疗提供新思路。

Alveolar epithelial cell injury, necrosis and regeneration abnormal changes are closely related to the pathogenesis of COPD, effectively repairing damaged alveolar epithelium has a decisive impact on the treatment and prognosis of COPD. Exogenous MSCs can differentiate into alveolar epithelial cells, and provide a new way for the treatment of COPD, but their poorly differentiation rate significantly hinders the application of MSCs. Wnt/β-catenin signaling pathway may play a key role in the regulation of epithelial differentiation of MSCs, intervention of Wnt/β-catenin signaling pathway may improve MSCs therapy to COPD.In this study, MSCs will be co-cultured with COPD alveolar epithelial cells in vitro, we will observe MSCs proliferation, invasion and alveolar epithelial differentiation through activating and inhibiting the Wnt/β-catenin signaling pathway. Then in COPD rat model, activating the Wnt/β-catenin signaling pathway as a starting point, transfecting Wnt3a gene into MSCs, we will observe how MSCs differentiate into alveolar epithelial cells and the structure and function of the alveolar epithelium through activating the Wnt/β-catenin signaling pathway,our study will provide a new basis on the Wnt/β-catenin signaling pathway in the MSCs -mediated alveolar epithelial repair and remodeling of COPD and new ideas for cell therapy of COPD.