Protective Effect of Demethylation Treatment on Cigarette Smoke Extract-Induced Mouse Emphysema Model
Protective Effect of Demethylation Treatment on Cigarette Smoke Extract-Induced Mouse Emphysema Model
复制标题
去甲基化治疗对香烟烟雾提取物所致小鼠肺气肿模型的保护作用
DOI：
10.1254/jphs.13072fp
复制
发表时间：
2013-10-01
影响因子：
3.5
通讯作者：
He, Zhihui
中科院分区：
文献类型：
--
作者：
Zhang, Hongliang;Chen, Ping;He, Zhihui
在本研究中，我们探讨了去甲基化在香烟烟雾提取物（CSE）诱导的小鼠肺气肿模型中的作用。将动物随机分为对照组、CSE组、5-氮杂-2 '-脱氧胞苷（AZA）组和CSE+AZA组（每组n = 10）。与对照组相比，CSE组的线粒体转录因子A（mtTFA）启动子甲基化增加了4倍以上，AZA可逆转这一趋势。与对照组相比，CSE组的mtTFA和细胞色素c氧化酶亚基II（考克斯II）mRNA和蛋白水平降低了约3倍，AZA在很大程度上恢复了这一水平。组织学分析显示，与对照组相比，CSE组表现出肺气肿，AZA可减轻肺气肿。此外，CSE还可明显诱导肺细胞凋亡，降低肺功能和肺线粒体功能。考克斯活性在AZA作用下大部分恢复。总之，我们首次提供证据表明，去甲基化治疗与AZA可以有效地改善肺气肿，肺功能，肺细胞凋亡，肺线粒体考克斯活性在CSE诱导的小鼠肺气肿模型，这增加了新的见解去甲基化剂在预防和治疗香烟烟雾诱导的肺气肿的治疗潜力。
In the present study, we explored the effects of demethylation in a cigarette smoke extract (CSE)-induced mouse emphysema model. Animals were randomly assigned to the control group, CSE group, 5-aza-2'-deoxycytidine (AZA) group, and CSE+AZA group (n = 10 per group). The mitochondrial transcription factor A (mtTFA) promoter methylation increased over 4-fold in the CSE group compared with the control group, which was reversed by AZA. The mtTFA and the cytochrome c oxidase subunit II (COX II) mRNA and protein levels were decreased approximately 3-fold in the CSE group compared with the control group, which was largely restored by AZA. Histological analysis showed that the CSE group exhibited emphysema compared with the control, which was alleviated by AZA. In addition, CSE significantly induced lung cell apoptosis and decreased lung function and lung mitochondria! COX activity, which was mostly restored by AZA. In conclusion, we for the first time provide evidence that demethylation therapy with AZA can effectively improve emphysema, lung function, lung cell apoptosis, and lung mitochondrial COX activity in a CSE-induced mouse emphysema model, which adds fresh insight into the therapeutic potential of demethylating agents in the prevention and treatment of cigarette smoke-induced emphysema.