Zhang Wan-Guang, Wu Si-Si, He Li, Yang Qun, Feng Yi-Kuan, Chen Yue-Tao, Zhen Guo-Hua, Xu Yong-Jian, Zhang Zhen-Xiang, Zhao Jian-Ping, Zhang Hui-Lan
Department of Surgery, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Respiratory and Critical Care Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, 1095, Jie Fang Road, Han Kou District, Wu Han City, HuBei Province 430030, China.
Acta Histochem. 2017 Apr;119(3):244-251. doi: 10.1016/j.acthis.2017.01.007. Epub 2017 Feb 21.
Combined pulmonary fibrosis and emphysema (CPFE) is an "umbrella term" encompassing emphysema and pulmonary fibrosis, but its pathogenesis is not known. We established two models of CPFE in mice using tracheal instillation with bleomycin (BLM) or murine gammaherpesvirus 68 (MHV-68). Experimental mice were divided randomly into four groups: A (normal control, n=6), B (emphysema, n=6), C (emphysema+MHV-68, n=24), D (emphysema+BLM, n=6). Group C was subdivided into four groups: C1 (sacrificed on day 367, 7 days after tracheal instillation of MHV-68); C2 (day 374; 14days); C3 (day 381; 21days); C4 (day 388; 28days). Conspicuous emphysema and interstitial fibrosis were observed in BLM and MHV-68 CPFE mouse models. However, BLM induced diffuse pulmonary interstitial fibrosis with severely diffuse pulmonary inflammation; MHV-68 induced relatively modest inflammation and fibrosis, and the inflammation and fibrosis were not diffuse, but instead around bronchioles. Inflammation and fibrosis were detectable in the day-7 subgroup and reached a peak in the day-28 subgroup in the emphysema + MHV-68 group. Levels of macrophage chemoattractant protein-1, macrophage inflammatory protein-1α, interleukin-13, and transforming growth factor-β1 in bronchoalveolar lavage fluid were increased significantly in both models. Percentage of apoptotic type-2 lung epithelial cells was significantly higher; however, all four types of cytokine and number of macrophages were significantly lower in the emphysema+MHV-68 group compared with the emphysema +BLM group. The different changes in pathology between BLM and MHV-68 mice models demonstrated different pathology subtypes of CPFE: macrophage infiltration and apoptosis of type-II lung epithelial cells increased with increasing pathology score for pulmonary fibrosis.
合并性肺纤维化和肺气肿（CPFE）是一个涵盖肺气肿和肺纤维化的“统称”，但其发病机制尚不清楚。我们通过气管内滴注博来霉素（BLM）或鼠γ疱疹病毒68（MHV-68）在小鼠中建立了两种CPFE模型。将实验小鼠随机分为四组：A组（正常对照组，n = 6）、B组（肺气肿组，n = 6）、C组（肺气肿+MHV-68组，n = 24）、D组（肺气肿+BLM组，n = 6）。C组再细分为四组：C1组（在气管内滴注MHV-68后第367天，即7天后处死）；C2组（第374天；14天）；C3组（第381天；21天）；C4组（第388天；28天）。在BLM和MHV-68 CPFE小鼠模型中均观察到明显的肺气肿和间质纤维化。然而，BLM诱导弥漫性肺间质纤维化并伴有严重的弥漫性肺部炎症；MHV-68诱导的炎症和纤维化相对较轻，且炎症和纤维化并非弥漫性的，而是围绕细支气管。在肺气肿+MHV-68组中，炎症和纤维化在第7天亚组中可检测到，并在第28天亚组中达到峰值。两种模型中支气管肺泡灌洗液中巨噬细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α、白细胞介素-13和转化生长因子-β1水平均显著升高。凋亡的2型肺上皮细胞百分比显著更高；然而，与肺气肿+BLM组相比，肺气肿+MHV-68组中所有四种细胞因子水平和巨噬细胞数量均显著更低。BLM和MHV-68小鼠模型之间病理变化的不同表明CPFE存在不同的病理亚型：随着肺纤维化病理评分的增加，巨噬细胞浸润和II型肺上皮细胞凋亡增加。
