Wnt5a及其受体在支气管扩张中的作用机制

The mechanism of Wnt5a and its receptor in bronchiectasis

目的 探索Wnt5a及其受体在支气管扩张(简称支扩)发病中的可能机制。方法 收集2017年10月—2018年4月四川大学华西医院呼吸与危重症医学科门诊确诊为支扩的患者,对照组为体检发现并在呼吸与危症重医学科门诊就诊的肺部结节(直径小于10 mm)需行支气管镜检查者,术中留取其健侧支气管黏膜作为正常对照组。所有受试者4周内未用抗生素及糖皮质激素,无其他呼吸道疾病。收集受试者的临床信息、血清标本及支气管黏膜标本。对支扩组与对照组患者血清标本的Wnt5a浓度采用酶联免疫吸附试验进行检测并比较其差异,对支气管黏膜中Wnt5a、其受体Ror2及其下游因子白细胞介素(interleukin,IL)-1β、IL-6的表达采用荧光实时定量聚合酶链反应进行检测。结果 本研究共收集了32例门诊支扩患者,排除15例,最终纳入17例支扩患者并完成临床试验,同时纳入18例因肺部结节行支气管镜检查者作为对照组。支扩组患者血清Wnt5a水平高于对照组患者(P<0.05),差异有统计学意义。将支扩患者血清Wnt5a浓度与C反应蛋白、血白细胞计数、血中性粒细胞比例、支气管扩张危重指数之间进行相关性分析,结果显示Wnt5a浓度与C反应蛋白的浓度呈正相关(r=0.806,P<0.05)。支扩组患者支气管黏膜的Wnt5a、Ror2、IL-1β、IL-6的mRNA相对表达量较对照组均显著升高(均P<0.05)。结论 Wnt5a基因可能通过Wnt5a/Ror2信号通路诱导巨噬细胞分泌炎症因子IL-1β、IL-6从而对炎症过程进行调控。

Objective To explore the potential roles and mechanism of Wnt5a and its receptors in the pathogenesis of bronchiectasis.Methods From October 2017 to April 2018,outpatients with bronchiectasis who needed bronchoscopy were recruited in the Department of Respiratory and Critical Care Medicine of West China Hospital of Sichuan University.The control group was patients with pulmonary nodules less than 10 mm in diameter by health inspection.Patients who used antibiotics and/or glucocorticoids within the past 4 weeks or had other airway diseases were excluded.Serum and bronchial mucosa were collected for detection of Wnt5a by enzyme-linked immunosorbent assay and real-time polymerase chain reaction(PCR),respectively.The receptor of Wnt5a,Ror2,and the downstream proinflammatory cytokines,interleukin(IL)-1β and IL-6,were measured in the bronchial mucosa by real-time PCR.Results From October 2017 to April 2018,32 outpatients with bronchiectasis were found but only 17 patients finished this study,and simultaneously 18 patients with pulmonary nodules were chosen as control.The level of serum Wnt5a in patients with bronchiectasis were significantly higher than that in the control group(P<0.05).Correlation analyses showed that serum Wnt5a level was positively correlated with the level of serum C reactive protein(r=0.806,P<0.05),but had no relation with the level of white blood cell count,blood neutrophil percentage,pulmonary function or bronchiectasis severe index.The mRNA levels of Wnt5a and its receptor Ror2 in bronchial mucosa of patients with bronchiectasis were significantly higher than those in the control group(P<0.001).The mRNA levels of IL-1β and IL-6 in bronchial mucosa of patients with bronchiectasis were higher than those in the control group(P<0.05).Conclusion Wnt5a may play crucial roles in the development of bronchiectasis through Wnt5a/Ror2 signaling pathways to regulate the release of proinflammatory cytokines including IL-1β and IL-6.