Deng Minhua, Li Jinhua, Gan Ye, Chen Yan, Chen Ping
Respiratory Medicine Department, PLA Rocket Force General Hospital, Beijing; Respiratory Medicine Department.
Respiratory Medicine Department.
Int J Chron Obstruct Pulmon Dis. 2017 Mar 14;12:861-872. doi: 10.2147/COPD.S129871. eCollection 2017.
COPD is a leading cause of mortality worldwide, and cigarette smoke is a pivotal risk factor. Adenovirus is a common cause of acute exacerbations of COPD and expedites COPD progression. Lung stem/progenitor cells play an important role in the development of COPD, while the relevant mechanism remains elusive. Here, we investigated the number of lung CD31CD45Sca-1 cells and sonic hedgehog (Shh) signaling pathway expression levels in cigarette smoke extract (CSE)-induced emphysema mice, as well as the relevant effects of acute adenovirus infection (AAI).
BALB/c mice were treated with CSE by intraperitoneal injection and/or adenovirus endotracheal instillation at different time points for 28 days. Lung function, lung histomorphology, CD31CD45Sca-1 cell count, and expression levels of major components in the Shh signaling pathway in the lungs were measured.
CSE intraperitoneal injection and adenovirus endotracheal instillation successfully induced emphysema and AAI in mice, respectively. In the lungs of emphysema mice, both the number of CD31CD45Sca-1 cells and expression levels of Shh signaling pathway molecules were reduced. However, AAI increased the number of inhibited CD31CD45Sca-1 cells and activated the suppression of the Shh signaling pathway.
Both CD31CD45Sca-1 cell numbers and Shh signaling pathway expression levels were downregulated in the lungs of emphysema mice induced by CSE intraperitoneal injection, which likely contributes to the pathogenesis of emphysema. Additionally, these inhibited lung CD31CD45Sca-1 cells and Shh signaling pathway molecules were upregulated during AAI, indicating that they play a protective role in the epithelial repair process after AAI injury.
慢性阻塞性肺疾病（COPD）是全球范围内主要的死亡原因之一，而香烟烟雾是一个关键的危险因素。腺病毒是COPD急性加重的常见原因，并加速COPD的进展。肺干细胞/祖细胞在COPD的发展中起重要作用，但其相关机制仍不清楚。在此，我们研究了香烟烟雾提取物（CSE）诱导的肺气肿小鼠肺中CD31⁺CD45⁻Sca-1⁺细胞的数量和音猬因子（Shh）信号通路的表达水平，以及急性腺病毒感染（AAI）的相关影响。
在不同时间点对BALB/c小鼠进行腹腔注射CSE和/或气管内滴注腺病毒，持续28天。检测小鼠的肺功能、肺组织形态学、CD31⁺CD45⁻Sca-1⁺细胞计数以及肺中Shh信号通路主要成分的表达水平。
腹腔注射CSE和气管内滴注腺病毒分别成功诱导了小鼠肺气肿和AAI。在肺气肿小鼠的肺中，CD31⁺CD45⁻Sca-1⁺细胞数量和Shh信号通路分子的表达水平均降低。然而，AAI增加了受抑制的CD31⁺CD45⁻Sca-1⁺细胞数量，并激活了对Shh信号通路的抑制。
腹腔注射CSE诱导的肺气肿小鼠肺中CD31⁺CD45⁻Sca-1⁺细胞数量和Shh信号通路表达水平均下调，这可能有助于肺气肿的发病机制。此外，在AAI期间，这些受抑制的肺CD31⁺CD45⁻Sca-1⁺细胞和Shh信号通路分子上调，表明它们在AAI损伤后的上皮修复过程中起保护作用。
