Expression of urocortin in rat lung and its effect on pulmonary vascular permeability.

Expression of urocortin in rat lung and its effect on pulmonary vascular permeability.
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尿皮质素在大鼠肺组织中的表达及其对肺血管通透性的影响

DOI:
10.1677/joe.1.06607
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发表时间:
2006-04
期刊:
The Journal of endocrinology
影响因子:
--
通讯作者:
--
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其他
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尿皮质素(Urocortin,UCN)是一种新发现的促肾上腺皮质激素释放激素(corticotropin-releasing hormone,CRH)结构相关肽,由40个氨基酸组成。逆转录聚合酶链反应(RT-PCR)检测UCN mRNA的表达。免疫组化和Western blot分析检测UCN肽。结果发现UCN mRNA和UCN肽在大鼠肺组织中均有明显表达。免疫组化结果显示UCN肽主要表达于支气管上皮、粘膜和肺泡上皮。我们还发现,吸入UCN大鼠肺血管通透性显着升高,与接受溶剂和卵清蛋白(OVA)的大鼠相比,通过伊文思蓝(EB)技术。光镜下HE染色可见UCN雾化吸入致肺充血水肿。非选择性肽类CRH受体拮抗剂astressin显著降低UCN引起的肺血管通透性。UCN诱导的肺血管通透性增强可分别被肥大细胞稳定剂克罗埃西亚和组胺-1(H1)受体拮抗剂氮卓斯汀预处理显著抑制,但不能被白三烯受体拮抗剂孟鲁司特抑制。总之,在本研究中,我们首次证明UCN在大鼠肺中表达,并通过激活CRH受体促进肺血管通透性增加。肥大细胞和组胺可能参与了UCN的这种作用。肺外周产生的UCN可能是一种自分泌和旁分泌的促炎因子。
Urocortin (UCN), a newly identified, 40-amino-acid, corticotropin-releasing hormone (CRH) structurally related peptide, has been demonstrated to be expressed in the central nervous system and many peripheral tissues of rats and man. This study aimed to investigate the expression profile of UCN in rat lung and the effect of UCN on lung vascular permeability. The expression of UCN mRNA was detected by reverse transcriptase PCR (RT-PCR). UCN peptide was measured by immunohistochemistry and Western blot analysis. We found that both UCN mRNA and peptide were obviously expressed in rat lung. Immunohistochemistry results showed that UCN peptide is mainly expressed in bronchial epithelium mucosa and alveolar epithelium. We also found that rats receiving inhalation aerosol of UCN had a significant elevation of lung vascular permeability compared with rats receiving vehicle and ovalbumin (OVA) by the Evans blue (EB) technique. UCN aerosol inhalation resulted in obvious pulmonary congestion and edema observed under light microscope by hematoxylin and eosin (HE) staining. The nonselective peptide CRH receptor antagonist astressin markedly reduced lung vascular permeability triggered by UCN. Enhanced pulmonary vascular permeability induced by UCN was markedly inhibited by pretreatment with the mast-cell stabilizer cromolyn and histamine-1 (H1) receptor antagonist azelastine respectively, but not by the leukotriene receptor antagonist montelukast. In summary, in the present study, we demonstrated for the first time that UCN is expressed in rat lung and contributes to an increase in lung vascular permeability through activation of CRH receptors. Mast cells and histamine may be involved in this effect of UCN. Peripherally produced UCN in lung may act as an autocrine and paracrine proinflammatory factor.
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