Zili Zhang1, Jian Wang2, Fei Liu1, Liang Yuan1, Mingjing Ding3, Lingdan Chen1, Jili Yuan4, Kai Yang1, Jing Qian3, Wenju Lu5. 1. 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. 2. 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. 3. Department of Respiratory Medicine, Inner Mongolia Autonomous Region People's Hospital, Hohhot 010017, Inner Mongolia Autonomous Region, China. 4. Department of Pediatrics, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China. 5. 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; Department of Laboratory Medicine, The First Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong 510180, PR China. Electronic address: wlu92@yahoo.com.
Abstract
AIMS: 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. MATERIALS AND METHODS: Rats were randomly assigned to NO2, NO2 + 5-Azacytidine, and normal air groups based on a emphysema rat model induced by chronic NO2 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 NO2 and normal air. KEY FINDINGS: 5-Azacytidine treatment led to restored ∆weight at 14 and 75 days of intervention and NO2 + 5-Azacytidine significantly reversed the effect of NO2 exposure on ∆weight. Intervention with 5-Azacytidine alleviated the decline of pulmonary function with a significant increase in FEV100/FVC% at 75 days in NO2 + 5-Azacytidine rats compared to NO2 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 NO2 + 5-Azacytidine rats. SIGNIFICANCE: This non-inflammatory rat emphysema model (induced by chronic NO2 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 NO2.
AIMS: A rat model of emphysema was established that mimics the features of the humanemphysema subtype and explores the effects of demethylation on lung function and blood tests. MATERIALS AND METHODS:Rats were randomly assigned to NO2, NO2 + 5-Azacytidine, and normal air groups based on a emphysemarat model induced by chronic NO2 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 NO2 and normal air. KEY FINDINGS:5-Azacytidine treatment led to restored ∆weight at 14 and 75 days of intervention and NO2 + 5-Azacytidine significantly reversed the effect of NO2 exposure on ∆weight. Intervention with 5-Azacytidine alleviated the decline of pulmonary function with a significant increase in FEV100/FVC% at 75 days in NO2 + 5-Azacytidinerats compared to NO2rats. 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 NO2 + 5-Azacytidinerats. SIGNIFICANCE: This non-inflammatory ratemphysema model (induced by chronic NO2 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 NO2.