Blocking of thromboxane A2 receptor attenuates airway mucus hyperproduction induced by cigarette smoke
Blocking of thromboxane A2 receptor attenuates airway mucus hyperproduction induced by cigarette smoke
复制标题
阻断血栓素 A2 受体可减轻香烟烟雾引起的气道粘液过度产生
DOI：
10.1016/j.ejphar.2013.01.042
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发表时间：
2013-03-05
影响因子：
5
通讯作者：
Wen, Fu-Qiang
中科院分区：
文献类型：
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作者：
An, Jing;Li, Ji-Qiong;Wen, Fu-Qiang
吸烟是慢性阻塞性肺疾病(COPD)的危险因素之一。在本研究中，我们研究了血栓素A(2)受体拮抗剂(TXA(2))对香烟烟雾诱导的呼吸道黏液产生的影响。大鼠暴露于香烟烟雾中，每天1小时，每周6天，持续4周。烟雾暴露前给予塞曲司特(2、5、10 mg/kg/d)灌胃。采用酶免疫法测定大鼠肺泡灌洗液和肺组织中血栓素B_2(TXB_2)的含量。采用碱性蛋白蓝/高碘酸盐法(AB-PAS)染色、Muc5ac免疫组织化学染色和RT-PCR法检测气道粘液产量。用Western blotting检测ERK和p38的磷酸化程度。塞曲司特减少支气管肺泡灌洗液和肺组织中TxB(2)的过量产生。香烟烟雾暴露显著增加大鼠气道AB/PAS染色的杯状细胞和Muc5ac的表达，塞曲司特可显著减弱这种作用。塞曲司特可减弱ERK和p38的磷酸化。TXA(2)受体拮抗剂在体内可通过丝裂原活化蛋白激酶(MAPK)信号通路减少吸烟诱导的Muc5ac的产生。(C)2013爱思唯尔B.V.保留所有权利。
Cigarette smoking is one of the risk factors for chronic obstructive pulmonary disease (COPD). In this study, we investigated the effects of thromboxane A(2) (TXA(2)) receptor antagonists on airway mucus production induced by cigarette smoke. Rats were exposed to cigarette smoke 1 h/day, 6 days/week for 4 weeks. Seratrodast (2, 5, 10 mg/kg day) was administered intragastrically prior to smoke exposure. Thromboxane B-2 (TXB2) in the bronchoalveolar lavage fluid and lung tissues was determined by enzyme immunoassay. Airway mucus production was determined by alcin-blue/periodic acid sthiff (AB-PAS) staining, Muc5ac immunohistochemical staining, and RT-PCR. The phosphorylation of ERK and p38 was evaluated by Western blotting. Seratrodast reduced the overproduction of TxB(2) in both bronchoalveolar lavage fluid and lung tissues. Cigarette smoke exposure markedly increased AB/PAS-stained goblet cells and rat Muc5ac expression in the airway, which was significantly attenuated by seratrodast administration. The induced phosphorylation of ERK and p38 was also attenuated by seratrodast. TxA(2) receptor antagonist could reduce Muc5ac production induced by cigarette smoke in vivo, possibly through the mitogen-activated protein kinases (MAPK) signaling pathway. (c) 2013 Elsevier B.V. All rights reserved.