红霉素对支气管哮喘大鼠Clara细胞及CC16表达的影响

Effect of erythromycin on Clara cell and Clara cell 16 000 protein in allergic asthmatic rats

目的探讨红霉素对支气管哮喘(简称哮喘)大鼠模型肺组织Clara细胞数量和Clara细胞分泌蛋白-16(CC16)表达的影响。方法用卵白蛋白(OVA)致敏、激发建立大鼠哮喘模型,随机分为正常对照组、哮喘组、红霉素组、地塞米松组。收集肺泡灌洗液(BALF)进行细胞计数及分类,光镜下观察肺组织病理学变化;ELISA方法检测BALF中CC16含量,用免疫组化的方法检测肺组织中Clara细胞表达变化。结果与正常对照组相比,哮喘组大鼠支气管及血管周围、肺间质内有嗜酸性粒细胞(EOS)及其他炎性细胞浸润,黏液腺增生,黏膜皱折增多,黏膜上皮细胞脱落,可见气道黏液栓,而红霉素组和地塞米松组上述现象明显减轻。肺组织Clara细胞计数显示,哮喘组大鼠终末及呼吸性细支气管上皮Clara细胞数明显少于正常对照组,而红霉素组和地塞米松组较哮喘组均有所增加(P<0.05)。哮喘组EOS百分比(EOS%)显著高于对照组(P<0.01),红霉素组和地塞米松组的EOS%均低于哮喘组(P<0.01)。BALF中CC16含量,哮喘组明显低于正常对照组(P<0.01),而红霉素组和地塞米松组均高于哮喘组(P<0.05)。结论哮喘时肺组织中Clara细胞及CC16的表达减少,红霉素可通过上调肺组织中Clara细胞及CC16的表达来发挥抗炎作用。

AIM To investigate the effects of erythromycin on the number of Clara cells and secretion of Clara cell 16 000 protein（CC16） in allergic asthmatic rats.METHODS A rat asthma model was established by sensitizing rats with ovalbumin,and the sensitized rats were randomly divided into the control group,asthma model group,erythromycin group and dexamethasone group.The histopathology of pulmonary tissues were observed by light microscope,and the concentrations of CC16 in bronchoalveolar lavage fluids（BALF） were measured by enzyme-linked immunosorbent assay （ELISA）.The total cell numbers,differential cell numbers were counted by different count fluids.The expression of Clara cell in pulmonary tissues was detected by immunohistochemistry（IHC）.RESULTS Compared with the control group,the lung tissues of asthma model group showed that there were eosinophil（EOS） and other inflammatory cells infiltration around the bronchus,vascular,bronchus mucus increased,airway epithelium damaged and desquamated and airway mucous plug,whereas erythromycin group and dexamethasone group showed significantly milder changes.Compared with the control group,the present of Clara cell in bronchial epithelium cells of asthma model group was significantly de- creased（P0.01）.The percent of both erythromycin group and dexamethasone group was higher than that of asthma model group（P0.05）.The percent of eosinophil cells in total cells（EOS%） in asthma model group was markedly higher than that in control group（P0.01）.Compared with asthma group,E0S%were all significantly decreased in erythromycin group and dexamethasone group（P0.01）.The concentrations of CC16 in BALF of asthma model group were significantly lower than those of control group（P0.01）.The protein concentrations in erythromycin group and dexamethasone group were all higher than those of asthma model group（P0.01）.CONCLUSION The number of Clara cells and secretion of CC16 protein in asthma are decreased.Erythromycin can increase the expression of Clara cells and CC16,suggesting that its anti-inflammatory effects may be partly through increasing the expression of CC16 in the lung tissue.