Non-inflammatory emphysema induced by NO2 chronic exposure and intervention with demethylation 5-Azacytidine
Non-inflammatory emphysema induced by NO2 chronic exposure and intervention with demethylation 5-Azacytidine
复制标题
NO2慢性暴露诱发的非炎性肺气肿及去甲基化5-氮杂胞苷干预
DOI：
10.1016/j.lfs.2019.02.022
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发表时间：
2019
期刊：
影响因子：
6.1
通讯作者：
Lu Wenju
中科院分区：
文献类型：
--
作者：
Zhang Zili;Wang Jian;Liu Fei;Yuan Liang;Ding Mingjing;Chen Lingdan;Yuan Jili;Yang Kai;Qian Jing;Lu Wenju
目的建立大鼠肺气肿模型，模仿人类肺气肿亚型的特征，探讨去甲基化对肺功能和血液tests.Materials和methodsRats的影响被随机分配到NO2，NO2+ 5-氮杂胞苷，和正常空气组的基础上慢性NO2暴露诱导的肺气肿大鼠模型。本研究通过分析支气管肺泡灌洗液（BALF）和血浆中的IL-6和TNF-α水平来评估肺气肿的特征。此外，CD 68巨噬细胞免疫荧光染色和BALF中的炎症细胞计数进行了比较暴露于NO2和正常空气。关键发现5-氮杂胞苷治疗导致在干预14和75天的体重恢复和NO2+ 5-氮杂胞苷显着逆转NO2暴露对体重的影响。5-氮杂胞苷干预后，NO2+ 5-氮杂胞苷组肺功能下降明显减轻，75 d时FEV 100/FVC%较NO2组显著增加。5-氮杂胞苷在第14天时降低了白色血细胞（WBC）、粒细胞、淋巴细胞和单核细胞计数，但在第45天时增加了WBC、粒细胞和单核细胞计数。NO2+ 5-Azacytidine大鼠的红细胞计数、血红蛋白和红细胞压积浓度显著降低。这些结果表明去甲基化剂用于预防和治疗由空气污染物NO2引起的肺气肿的治疗潜力。
AimsA 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 methodsRats were randomly assigned to NO2, NO2+ 5-Azacytidine, and normal air groups based on a emphysema rat model induced by chronic NO2exposure. 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 NO2and normal air.Key findings5-Azacytidine treatment led to restored ∆weight at 14 and 75 days of intervention and NO2+ 5-Azacytidine significantly reversed the effect of NO2exposure 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 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-Azacytidine rats.SignificanceThis non-inflammatory rat emphysema model (induced by chronic NO2exposure 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.