Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice.
Cigarette Smoke-Induced Emphysema and Pulmonary Hypertension Can Be Prevented by Phosphodiesterase 4 and 5 Inhibition in Mice.
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DOI：
10.1371/journal.pone.0129327
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Weissmann N
中科院分区：
文献类型：
--
作者：
Seimetz M;Parajuli N;Pichl A;Bednorz M;Ghofrani HA;Schermuly RT;Seeger W;Grimminger F;Weissmann N
慢性阻塞性肺疾病（COPD）是一种广泛存在的疾病，目前尚无有效的治疗方法。最近的研究结果表明，NO和sGC-cGMP信号转导的疾病的发病机制的关键作用。先前的数据表明产生可溶性鸟苷酸环化酶的cGMP的下调/失活，并且sGC刺激防止了小鼠中香烟烟雾诱导的肺气肿和肺动脉高压（PH）。因此，我们旨在研究cGMP降解磷酸二酯酶（PDE）5的抑制是否具有类似的效果。将结果与PDE 4抑制剂（cAMP升高）和两者组合的效果进行比较。C57 BL 6/J小鼠长期暴露于香烟烟雾，并平行接受他达拉非（PDE 5抑制剂）、吡拉米司特（PDE 4抑制剂）或两者治疗。功能测量（肺顺应性，血流动力学）和结构调查（肺泡和血管形态测定）以及心脏比率后，6个月的烟草烟雾暴露。此外，对各肺中肺泡巨噬细胞的数量进行计数。他达拉非、匹拉米司特或两者联合预防性治疗几乎完全预防了吸烟引起的肺气肿、肺顺应性增加、潮气量增加、肺血管结构重塑、右心室收缩压和右心室肥大。单药治疗可预防或减少吸烟诱导的肺泡巨噬细胞增加，但不能联合治疗。香烟烟雾诱导的肺气肿和PH可以通过抑制小鼠的磷酸二酯酶4和5来预防。
Chronic obstructive pulmonary disease (COPD) is a widespread disease, with no curative therapies available. Recent findings suggest a key role of NO and sGC-cGMP signaling for the pathogenesis of the disease. Previous data suggest a downregulation/inactivation of the cGMP producing soluble guanylate cyclase, and sGC stimulation prevented cigarette smoke-induced emphysema and pulmonary hypertension (PH) in mice. We thus aimed to investigate if the inhibition of the cGMP degrading phosphodiesterase (PDE)5 has similar effects. Results were compared to the effects of a PDE 4 inhibitor (cAMP elevating) and a combination of both. C57BL6/J mice were chronically exposed to cigarette smoke and in parallel either treated with Tadalafil (PDE5 inhibitor), Piclamilast (PDE4 inhibitor) or both. Functional measurements (lung compliance, hemodynamics) and structural investigations (alveolar and vascular morphometry) as well as the heart ratio were determined after 6 months of tobacco smoke exposure. In addition, the number of alveolar macrophages in the respective lungs was counted. Preventive treatment with Tadalafil, Piclamilast or a combination of both almost completely prevented the development of emphysema, the increase in lung compliance, tidal volume, structural remodeling of the lung vasculature, right ventricular systolic pressure, and right ventricular hypertrophy induced by cigarette smoke exposure. Single, but not combination treatment prevented or reduced smoke-induced increase in alveolar macrophages. Cigarette smoke-induced emphysema and PH could be prevented by inhibition of the phosphodiesterases 4 and 5 in mice.
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影响因子：
5.8
作者：
Ferrer E;Peinado VI;Díez M;Carrasco JL;Musri MM;Martínez A;Rodríguez-Roisin R;Barberà JA
通讯作者：
Barberà JA
DOI：
10.1164/rccm.200907-0988oc
发表时间：
2010-02-01
影响因子：
24.7
作者：
Blanco, Isabel;Gimeno, Elena;Albert Barbera, Joan
通讯作者：
Albert Barbera, Joan
影响因子：
3.2
作者：
Alp, S.;Skrygan, M.;Bastian, A.
通讯作者：
Bastian, A.
影响因子：
4.8
作者：
Fukao, M;Mason, HS;Keef, KD
通讯作者：
Keef, KD
影响因子：
24.3
作者：
Dony, E.;Lai, Y-J.;Schermuly, R. T.
通讯作者：
Schermuly, R. T.