State Key Laboratory of Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China.
State Key Laboratory of Respiratory Disease, Guangdong Key Laboratory of Vascular Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China; Division of Translational and Regenerative Medicine, Department of Medicine, The University of Arizona, Tucson, AZ 85721-0202, USA.
Life Sci. 2019 Mar 15;221:121-129. doi: 10.1016/j.lfs.2019.02.022. Epub 2019 Feb 11.
A rat model of emphysema was established that mimics the features of the human emphysema subtype and explores the effects of demethylation on lung function and blood tests.
Rats were randomly assigned to NO, NO + 5-Azacytidine, and normal air groups based on a emphysema rat model induced by chronic NO exposure. This study estimates the characteristics of emphysema by conducting an analysis for IL-6 and TNF-α levels in bronchoalveolar lavage fluids (BALF) and plasma. Furthermore, CD68 macrophage immunofluorescent staining and inflammatory cell counts in BALF were compared between rats exposed to NO and normal air.
5-Azacytidine treatment led to restored ∆weight at 14 and 75 days of intervention and NO + 5-Azacytidine significantly reversed the effect of NO exposure on ∆weight. Intervention with 5-Azacytidine alleviated the decline of pulmonary function with a significant increase in FEV100/FVC% at 75 days in NO + 5-Azacytidine rats compared to NO rats. 5-Azacytidine reduced the counts of white blood cells (WBCs), granulocytes, lymphocytes, and monocytes at 14 days, but increased WBC, granulocyte, and monocyte counts at 45 days. Red blood cell counts, hemoglobin, and hematocrit concentrations were significantly reduced in NO + 5-Azacytidine rats.
This non-inflammatory rat emphysema model (induced by chronic NO exposure with global DNA hypomethylation and demethylation therapy with 5-Azacytidine) effectively improved emphysema by alleviating the decline of lung function and hypoxia, and slightly reinforced immune function. These results indicate the therapeutic potential of demethylation agents for the prevention and treatment of emphysema induced by the air pollutant NO.
建立一种模拟人类肺气肿亚型特征的肺气肿大鼠模型，并探讨去甲基化对肺功能和血液检测的影响。
根据慢性一氧化氮（NO）暴露诱导的肺气肿大鼠模型，将大鼠随机分为 NO、NO+5-氮杂胞苷（5-Azacytidine）和正常空气组。本研究通过分析支气管肺泡灌洗液（BALF）和血浆中的白细胞介素 6（IL-6）和肿瘤坏死因子-α（TNF-α）水平来评估肺气肿的特征。此外，还比较了暴露于 NO 和正常空气的大鼠 BALF 中的 CD68 巨噬细胞免疫荧光染色和炎症细胞计数。
5-Azacytidine 治疗导致干预后第 14 天和第 75 天的体重恢复，NO+5-Azacytidine 显著逆转了 NO 暴露对体重的影响。与 NO 组相比，5-Azacytidine 干预减轻了 NO+5-Azacytidine 大鼠的肺功能下降，第 75 天的用力呼气量（FEV1）/用力肺活量（FVC）%显著增加。5-Azacytidine 降低了白细胞（WBC）、粒细胞、淋巴细胞和单核细胞计数在第 14 天，但增加了 WBC、粒细胞和单核细胞计数在第 45 天。NO+5-Azacytidine 大鼠的红细胞计数、血红蛋白和血细胞比容浓度显著降低。
本研究建立了一种非炎症性大鼠肺气肿模型（由慢性 NO 暴露引起，具有全基因组低甲基化和 5-Azacytidine 去甲基化治疗），通过改善肺功能下降和缺氧，有效缓解了肺气肿，轻度增强了免疫功能。这些结果表明，去甲基化剂在预防和治疗由空气污染物 NO 引起的肺气肿方面具有潜在的治疗作用。
