Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema
Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema
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DOI：
10.1152/ajplung.90270.2008
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发表时间：
2009-04-01
影响因子：
4.9
通讯作者：
Kubo, Keishi
中科院分区：
文献类型：
--
作者：
Chen, Yan;Hanaoka, Masayuki;Kubo, Keishi
[10] Chen Y，Hanaoka M，Chen P，Droma Y，Voelkel NF，Kubo K.贝前列素钠（一种稳定的前列环素类似物）对香烟烟雾提取物诱发肺气肿的保护作用。美国生理学杂志肺细胞分子生理学296：L 648-L 656，2009年。首次发表于2009年2月6日; doi：10.1152/ajplung.90270.2008。慢性炎症、蛋白水解和抗蛋白水解活性的失衡、氧化应激和肺结构细胞的凋亡有助于COPD的发病机制。前列环素保护细胞免于凋亡，具有抗炎特性，部分防止香烟烟雾提取物（CSE）诱导的肺内皮细胞凋亡，因此可能与肺气肿的发病机制相关。我们确定了一种合成的稳定的前列环素类似物贝前列素钠（BPS）是否能减弱CSE诱导的肺气肿的发展，并阐明了其作用的分子机制。用BPS处理Sprague-Dawley大鼠，每周注射一次CSE，持续3周。检测细胞DNA损伤、caspase-3表达、基质金属蛋白酶（MMP）-2和MMP-9活性。我们还分析了TNF α和IL-1 β浓度以及血清抗氧化活性。BPS阻止了CSE诱导的肺气肿的发展，导致肺泡扩大和肺实质破坏的显着衰减。BPS抑制肺细胞凋亡和诱导MMP-2和MMP-9活性。此外，BPS的保护作用与促炎细胞因子（包括TNF α和IL-1 β）表达的减少以及正常化的生物氧化剂活性有关。BPS可能通过作用于特定的前列环素受体激活cAMP信号传导而引入所有这些事件。总之，BPS通过减弱细胞凋亡、抑制蛋白水解酶活性、降低炎性细胞因子水平和增强抗氧化活性来防止CSE诱导的肺气肿的发展。BPS有可能成为预防人类肺气肿的新的治疗选择，具有前景。
Chen Y, Hanaoka M, Chen P, Droma Y, Voelkel NF, Kubo K. Protective effect of beraprost sodium, a stable prostacyclin analog, in the development of cigarette smoke extract-induced emphysema. Am J Physiol Lung Cell Mol Physiol 296: L648-L656, 2009. First published February 6, 2009; doi:10.1152/ajplung.90270.2008. Chronic inflammation, imbalance of proteolytic and anti-proteolytic activities, oxidative stress, and apoptosis of lung structural cells contribute to the pathogenesis of COPD. Prostacyclin protects cells against apoptosis, has anti-inflammatory properties, partially prevents cigarette smoke extract (CSE)-induced apoptosis of the pulmonary endothelium, and thus may be relevant in the pathogenesis of emphysema. We determined whether a synthetic stable prostacyclin analog, beraprost sodium (BPS), attenuates the development of CSE-induced emphysema and elucidated the molecular mechanisms involved in its effect. Sprague-Dawley rats were treated with BPS and injected with CSE once a week for 3 wk. We measured the DNA damage of cells, the expression of caspase-3, and the activity of matrix metalloproteinase (MMP)-2 and MMP-9. We also analyzed TNF alpha and IL-1 beta concentrations and the serum antioxidant activity. BPS prevented the development of CSE-induced emphysema, resulting in significant attenuation in alveolar enlargement and pulmonary parenchymal destruction. BPS inhibited pulmonary apoptosis and induction of MMP-2 and MMP-9 activity. Moreover, the protective effect of BPS was associated with a reduction of the expression of proinflammatory cytokines including TNF alpha and IL-1 beta and a normalized biological oxidant activity. BPS introduces all these events, probably by activating cAMP signaling through acting specific prostacyclin receptors. In conclusion, BPS protects against the development of CSE-induced emphysema by attenuating apoptosis, inhibiting proteolytic enzyme activity, reducing inflammatory cytokine levels, and augmenting antioxidant activity. BPS may potentially represent a new therapeutic option in the prevention of emphysema in humans in prospect.