哮喘联盟

   摘要
   背景：血管重塑在哮喘和慢性阻塞性肺病（COPD）中扮演者重要的角色。缓激肽（BK）是一个介导哮喘急性反应的血管活性促炎肽。我们研究哮喘和COPD中血管生成因子作用与BK受体的关系。
   方法：33例COPD患者，24例老年（≥50岁）哮喘（≥50年）患者，18例老年吸烟对照者，11例老年不吸烟对照者，15例年轻（≤40岁）哮喘（≤40年）患者，10例年轻不吸烟对照者的支气管活检标本采用免疫荧光染色法检测CD31、血管内皮生长因子-A（VEGF-A），血管生成素和BK受体（B2R和B1R）。免疫荧光法检测纤维母细胞和相关分子的内皮共定位。ELISA法对哮喘和COPD患者支气管纤维母细胞内的BK介导VEGF-A和血管生成素的释放情况进行研究。
   结果：在老年哮喘患者的支气管粘膜固有层，CD31和VEGF-A(+)细胞数高于老年不吸烟对照者（P<0.05）。老年哮喘患者的血管生成素(+)、B2R(+) 和B1R(+)细胞数高于老年不吸烟对照者、吸烟对照者和COPD患者（P<0.01）。COPD患者的血管生成素(+)细胞数均高于两个老年对照组（P<0.05）。在所有哮喘患者中，B2R(+)细胞数与B1R(+)细胞数（rs=0.43）、血管生成素(+)细胞数（rs=0.42）和CD31细胞（rs=0.46）明显相关（P<0.01）。血管生成素(+)细胞数与1s用力呼气量无明显相关性(rs=-0.415, P=0.008)。双免疫荧光法显示毛细血管CD31细胞与B2R共表达，纤维母细胞与B2R、 VEGF-A和血管生成素共表达。BK (10(-6)M)导致哮喘和COPD患者（程度较哮喘轻）的纤维母细胞内明显的血管生成素释放。
   结论：不同于COPD，本研究提示BK受体参与了哮喘患者支气管血管的重塑过程。
 

（刘国梁 审校）
Thorax. 2013 Sep;68(9):803-11. doi: 10.1136/thoraxjnl-2012-202741. Epub 2013 Jun 5.


 

Expression of vascular remodelling markers in relation to bradykinin receptors in asthma and COPD.
 

Ricciardolo FL, Sabatini F, Sorbello V, Benedetto S, Defilippi I, Petecchia L, Usai C, Gnemmi I, Balbi B, De Rose V, Ten Hacken NH, Postma DS, Timens W, Di Stefano A.
 

ABSTRACT
BACKGROUND: Vascular remodelling plays a central role in asthma and chronic obstructive pulmonary disease (COPD). Bradykinin (BK) is a vasoactive proinflammatory peptide mediating acute responses in asthma. We investigated the role of angiogenic factors in relation to BK receptors in asthma and COPD.
METHODS: Bronchial biopsies from 33 patients with COPD, 24 old (≥50 years) patients with (≥50 years) asthma, 18 old control smokers, 11 old control non-smokers, 15 young (≤40yrs) patients with (≤40 years) asthma and 10 young control non-smokers were immunostained for CD31, vascular endothelial growth factor-A (VEGF-A), angiogenin and BK receptors (B2R and B1R). Fibroblast and endothelial co-localisation of relevant molecules were performed by immunofluorescence. BK-induced VEGF-A and angiogenin release was studied (ELISA) in bronchial fibroblasts from subjects with asthma and COPD.
RESULTS: In bronchial lamina propria of old patients with asthma, CD31 and VEGF-A(+) cell numbers were higher than old control non-smokers (p<0.05). Angiogenin(+), B2R(+) and B1R(+) cell numbers in old patients with asthma were higher than in old control non-smokers, control smokers and patients with COPD (p<0.01). Angiogenin(+) cell numbers were higher in patients with COPD than both old control groups (p<0.05). In all patients with asthma the number of B2R(+) cells was positively related to the numbers of B1R(+) (rs=0.43), angiogenin(+) (rs=0.42) and CD31 cells (rs=0.46) (p<0.01). Angiogenin(+) cell numbers were negatively related to forced expiratory volume in 1 s (rs=-0.415, p=0.008). Double immunofluorescence revealed that CD31 cells of capillary vessels coexpressed B2R and that fibroblasts coexpressed B2R, VEGF-A and angiogenin. BK (10(-6)M) induced significant angiogenin release in fibroblasts from asthma and to a lesser extent in COPD.
CONCLUSIONS: Unlike COPD, this study suggests the involvement of BK receptors in bronchial vascular remodelling in asthma.
 

Thorax. 2013 Sep;68(9):803-11. doi: 10.1136/thoraxjnl-2012-202741. Epub 2013 Jun 5.