卡介苗对支气管哮喘大鼠气道重塑及血清HIF-1α表达的影响

    Effect of BCG on the airway remodeling and serum level of HIF-1α in bronchial asthma rats

    • 摘要:
      目的探讨卡介苗(BCG)干预下,支气管哮喘大鼠气道重塑以及血清缺氧诱导因子-1α(HIF-1α)的表达情况。
      方法将30只清洁级健康雄性Sprague-Dawley(SD)大鼠随机分为对照组、哮喘组和BCG治疗组,每组10只。哮喘组大鼠采用腹腔注射10%卵白蛋白(OVA)+氢氧化铝混合液致敏,再用1% OVA超声雾化吸入的方法进行激发制作支气管哮喘模型;对照组大鼠采用相同的制模方法,但在相应的时间点使用0.9%氯化钠溶液替代致敏剂,进行腹腔注射和超声雾化吸入处理。BCG治疗组大鼠制模方法与哮喘组相同,每天雾化前半小时皮内注射BCG 0.025 mg进行干预治疗。3组大鼠在末次激发24 h后收集血清标本,采用ELISA法检测HIF-1α含量,采血后处死大鼠并制作气管和肺组织病理切片,观察大鼠气道炎症及气管重塑情况。运用图像分析软件测量支气管内径周长(Pi)、支气管管壁面积(WAt)、支气管平滑肌总面积(WAm)等指标, 并与Pi比较进行标化。
      结果对照组大鼠肺组织中肺泡、气管、血管结构均正常;哮喘组大鼠肺泡壁明显增厚,气管腔可见黏液残留,部分可见肺泡腔内出血;BCG治疗组大鼠肺组织整体结构趋于正常。哮喘组大鼠血清中HIF-1α含量较对照组升高,经BCG干预后,大鼠血清HIF-1α降低(P < 0.01)。HIF-1α和支气管壁厚度(WAt/Pi)之间的相关性呈正相关,和支气管平滑肌厚度(WAm/Pi)之间的相关性呈正相关(P < 0.01)。
      结论支气管哮喘大鼠经过BCG干预治疗,气道重塑减轻,可能是通过抑制HIF-1α的表达来发挥作用。

       

      Abstract:
      ObjectiveTo investigate the effects of BCG intervention on the airway remodeling and serum hypoxia-inducible factor-1 alpha(HIF-1α)expression in bronchial asthma rats.
      MethodsThirtySD rats were randomly divided into the control group, asthma group and BCG treatment group(10 rats each group).The asthma group were intraperitoneally injected with 10% egg albumin(OVA)combined with aluminum hydroxide mixture for sensitization, and then stimulated by 1% OVA ultrasonic atomization inhalation to establish bronchial asthma model.The control group were treated with the same establishing model method, but at the corresponding time point, 0.9% sodium chloride solution was used to replace the sensitizer, and intraperitoneal injection and ultrasonic atomization inhalation were performed.The modeling method in BCG treatment group were the same as that of the asthma group, and the intradermal injection of 0.025 mg of BCG before half an hour of atomization was performed daily for intervention treatment.The inter-group variables were analyzed using Pearson correlation analysis method.The serum samples were collected after 24 h of last stimulation in three groups, and the contents of HIF-1α were detected using ELISA.After the rats were sacrificed, the trachea and lung histopathology sections were made to observe the airway inflammation and tracheal remodeling.The image analysis software was used to measure the internal diameter circumference(Pi), bronchial tube wall area(WAt)and total area of bronchial smooth muscle(WAm).
      ResultsThe structures of alveoli, trachea and blood vessels in control group were normal.In the asthma group, the alveolar wall significantly thickened, mucus remained in the trachea cavity, and intra-alveolar hemorrhage was partially observed.The overall structure of lung tissues in BCG treatment group tended to be normal.The serum HIF-1α content in asthma group increased compared with the control group, and the serum HIF-1 content decreased after BCG intervention(P < 0.01).The HIF-1α was positively correlated with bronchial wall thickness(WAt/Pi)and bronchial smooth muscle thickness(WAm/Pi)(P < 0.01).
      ConclusionsAfter BCG intervention treatment, the airway remodeling alleviates in bronchial asthma rats, and the effects may be by inhibiting HIF-1α expression to play.

       

    /

    返回文章
    返回