Beraprost sodium attenuates cigarette smoke extract-induced apoptosis in vascular endothelial cells
Beraprost sodium attenuates cigarette smoke extract-induced apoptosis in vascular endothelial cells
复制标题
贝前列素钠减弱香烟烟雾提取物诱导的血管内皮细胞凋亡
DOI：
10.1007/s11033-012-1924-1
复制
发表时间：
2012-12-01
影响因子：
2.8
通讯作者：
Chen, Ping
中科院分区：
文献类型：
--
作者：
Chen, Yan;Luo, Hong;Chen, Ping
细胞凋亡是慢性阻塞性肺疾病（COPD）发病机制的重要组成部分。我们之前的研究表明，前列环素（PGI2）类似物（beraprost钠，BPS）可以阻止香烟烟雾提取物（CSE）诱导的大鼠肺内皮细胞凋亡。因此，我们决定明确COPD患者血管内皮细胞的凋亡情况以及前列环素对CSE诱导的血管内皮细胞凋亡的保护作用。12例COPD患者和10例对照组的手术标本，检测细胞凋亡水平、前列环素合成酶（PGI2S）表达水平和PGI2稳定代谢物6-酮- pgf1 α （PGI2的稳定代谢物）水平。研究了暴露于不同浓度CSE 24 h和暴露于2.5% CSE不同时间的人脐静脉内皮细胞（HUVECs）的凋亡指数（AI）、caspase-3活性、caspase-3和6-酮- pgf1 α的表达。然后，在2.5% CSE条件下，将HUVECs暴露于不同浓度的BPS中24 h，观察cAMP的变化和水平。与对照组相比，COPD患者肺部AI升高，PGI2S和6-酮- pgf1 α表达降低。此外，CSE以剂量依赖性和时间依赖性的方式诱导细胞凋亡，并降低huvec中6-keto-PGF1α的水平。BPS处理后，细胞内cAMP水平升高，细胞凋亡减少。pgi2的缺乏对copd相关的内皮功能障碍和细胞凋亡至关重要。BPS对CSE诱导的血管内皮细胞凋亡具有保护作用。
Apoptosis is now widely recognized as an important part of chronic obstructive pulmonary disease (COPD) pathogenesis. Our previous study demonstrated that a prostacyclin (PGI2) analogue (beraprost sodium, BPS) prevented cigarette smoke extract (CSE) induced apoptosis of the pulmonary endothelium in rats. So we determined to clarify the apoptosis of vascular endothelial cells in COPD patient and the role of prostacyclin in the protection against apoptosis in vascular endothelial cells induced by CSE. Surgical specimens were obtained from 12 patients with COPD and 10 controls, and the level of apoptosis, prostacyclin synthase (PGI2S) expression and 6-keto-PGF1α (a stable metabolite of PGI2) were detected. The apoptotic index (AI), caspase-3 activity, expression of caspase-3 and 6-keto-PGF1α were examined in human umbilical vein endothelial cells (HUVECs) under exposure to varied concentrations of CSE for 24 h as well as under exposure to 2.5 % CSE for varied durations. Then, HUVECs under 2.5 % CSE were exposed to varied concentrations of BPS for 24 h and observed the alteration and the level of cAMP. Increased AI, decreased expression of PGI2S and 6-keto-PGF1α, were found in the lungs of patients with COPD compared with controls. Moreover, CSE induced apoptosis in means of both dose-dependent and time-dependent manners, and reduced the level of 6-keto-PGF1α in HUVECs. And with the treatment of BPS, an enhanced level of cAMP and decreased apoptosis were detected. The deficiency of PGI2critically contributes to the COPD-associated endothelial dysfunction and apoptosis. And BPS protects against the apoptosis in the vascular endothelial cells induced by CSE.