He Zhi-Hui, Chen Yan, Chen Ping, He Sheng-Dong, Zeng Hui-Hui, Ye Ji-Ru, Liu Da, Cao Jun
Intensive Care Unit.
Department of Respiratory Medicine, Second Xiangya Hospital, Central South University, Changsha.
Int J Chron Obstruct Pulmon Dis. 2017 Oct 30;12:3149-3158. doi: 10.2147/COPD.S131090. eCollection 2017.
There is a growing realization that COPD, or at least emphysema, involves several processes presenting in aging and cellular senescence. Endothelial progenitor cells (EPCs) contribute to neovascularization and play an important role in the development of COPD. The gene for p16 is a major dominant senescence one. The aim of the present study was to observe changes in lung function, histomorphology of lung tissue, and expression of p16 in lung tissue and bone marrow-derived EPCs in emphysematous mice induced by cigarette-smoke extract (CSE), and further to search for a potential candidate agent protecting against emphysema induced by CSE.
An animal emphysema model was induced by intraperitoneal injection of CSE. 5-Aza-2'-deoxycytidine (5-Aza-CdR) was administered to the emphysematous mice. Lung function and histomorphology of lung tissue were measured. The p16 protein and mRNA in EPCs and lung tissues were detected using Western blotting and quantitative reverse-transcription polymerase chain reaction, respectively.
CSE induced emphysema with increased p16 expression in lung tissue and bone marrow-derived EPCs. 5-Aza-CdR partly protected against emphysema, especially in the lung-morphology profile, and partly protest against the overexpression of p16 in EPCs and lung tissue induced by CSE.
5-Aza-CdR partly protected against emphysema in mice via suppressing p16 expression in EPCs and lung tissue.
人们越来越认识到慢性阻塞性肺疾病（COPD），或者至少是肺气肿，涉及衰老和细胞衰老中出现的几个过程。内皮祖细胞（EPCs）有助于新血管形成，并在COPD的发展中发挥重要作用。p16基因是主要的显性衰老基因。本研究的目的是观察香烟烟雾提取物（CSE）诱导的肺气肿小鼠的肺功能、肺组织形态学变化以及肺组织和骨髓来源的EPCs中p16的表达，并进一步寻找一种潜在的预防CSE诱导的肺气肿的候选药物。
通过腹腔注射CSE诱导动物肺气肿模型。对肺气肿小鼠给予5-氮杂-2'-脱氧胞苷（5-Aza-CdR）。检测肺功能和肺组织形态学。分别使用蛋白质免疫印迹法和定量逆转录聚合酶链反应检测EPCs和肺组织中的p16蛋白和mRNA。
CSE诱导肺气肿，导致肺组织和骨髓来源的EPCs中p16表达增加。5-Aza-CdR部分预防了肺气肿，尤其是在肺形态方面，并且部分对抗了CSE诱导的EPCs和肺组织中p16的过表达。
5-Aza-CdR通过抑制EPCs和肺组织中p16的表达部分预防了小鼠肺气肿。
