红霉素在慢性阻塞性肺疾病中的作用及其机制  

Role and Mechanism of Erythromycin in Chronic Obstructive Pulmonary Disease

作　　者：林芃[1] 白晶[1] 钟小宁[1] 梁国容[1] 梁向东[1] 张健全[1] 

机构地区：[1]广西医科大学第一附属医院呼吸内科,南宁530021

出　　处：《中国药学杂志》2008年第13期978-981,共4页Chinese Pharmaceutical Journal

基　　金：广西科学基金(桂科基0448054);广西医疗卫生重点科研课题(重200401)

摘　　要：目的探讨红霉素在慢性阻塞性肺疾病中的作用及其机制。方法复制慢性支气管炎和肺气肿大鼠动物模型,用红霉素治疗和预防治疗。采用HE染色观察病理形态学变化,Masson染色观察肺细小支气管结构改变,采用ELISA法测定血清中IL-IO、INF-γ以及血清和肺泡灌洗液(BALF)中TNF-α的浓度,采用放免法测定血清和BALF中PCⅢ、HA水平。结果给予红霉素治疗和预防治疗后,BALF中的中性粒细胞数百分比明显低于模型组,气道壁、气管腔内的炎症反应减轻,红霉素预防治疗后细支气管中膜肌层面积和厚度显著减少,血清和BALF中PCⅢ和HA水平显著下降,均低于模型组,加药组与模型组比较,IL-10分泌无明显变化,INF-γ分泌降低,但是INF-γ/IL-10比例无显著性差异。结论红霉素能够部分的减轻气道腔内炎症反应,改善中膜肌层增厚与细胞外基质沉积,纠正气道重塑。其机制主要与通过抑制炎细胞聚集与活化,抑制炎细胞分泌和释放细胞外基质。红霉素可作为在慢性阻塞性肺疾病(COPD)疾病早期预防气道重塑和降低气道慢性炎症的药物。OBJECTIVE To investigate the role and the mechanism of erythromycin in chronic obstructive pulmonary disease. METHODS Rat mode with chronic bronchitis （CB） and emphysema was established. The protective and therapeutic effects of erythromycin（ EM ） were evaluated. The pathomorphological changes of bronchi and bronchioles with masson staining were observed by morphometry analysis. The levels of interleukin-10 （IL-10） and interferon-γ（INF-γ） in serum and tumor necrosis factor-α（TNF-α） in serum and bronchoalveolar lavage fluid （ BALF ） were detected by ELISA . The levels of hyaluronic acid （ HA ） and procollagen type Ⅲ （PC Ⅲ） in serum and BALF were detected by radioimmunoassay. RESULTS After treatment or prevention with EM, the percentages of neutrophils in BALF of model group were higher than those of control group. The inflammation on airway wall and airway lumen was significantly decreased. The thickness of the smooth muscles and collagen in the bronchial wall and the levels of PC Ⅲ and HA in serum and the levels of PC Ⅲ and HA in BALF were reduced, compared with those in model group. The levels of IL-10 were not significantly different and the levels of INF-γ were significantly decreased, but the ratio of INF-γ and IL-10 were not significantly different between before and after treatment or prevention with EM, compared with those in model group. CONCLUSION EM may prevent airway intraluminal inflammation and inhibit the airway remodeling by inducing the thickeness of the smooth muscles in the bronchial wall and the apposition of ECM. The principle might be that erythromycin could inhibit the aggregation and activation of inflammatory cells, and release ECM. EM could be used as a medicine to prevent airway remodeling and induce chronic inflammation on airway on earlier period of COPD.

关 键 词：红霉素 慢性阻塞性 肺疾病 

分 类 号：R446.62[医药卫生—诊断学]