多西环素对哮喘大鼠气道炎症及气道重塑的影响

摘要

目的：探讨多西环素对哮喘大鼠气道炎症及重塑的预防作用及可能机制。方法将实验 SD 大鼠分为正常对照组、哮喘组、多西环素干预组。计数大鼠肺泡灌洗液中的细胞数并进行分类；检测血清中的白细胞介素5(IL-5)、白细胞介素13(IL-13)、肿瘤坏死因子α(TNF-α)的水平；检测肺组织中基质金属蛋白酶9(MMP-9)、肌动蛋白α(α-SMA)的表达；测定支气管基底膜周径(Pbm)、总管壁面积(WAt)、平滑肌面积(WAm)等反映气道壁厚度的指标，分析多西环素的影响。结果哮喘组与多西环素干预组的肺泡灌洗液细胞总数、嗜酸性粒细胞计数、支气管壁厚度、平滑肌厚度、血清 IL-5、IL-13及 TNF-α水平、肺组织 MMP-9、α-SMA 平均光度值均明显高于正常对照组，其中多西环素干预组均明显低于哮喘组(P <0.05)。结论多西环素可以影响炎症介质的生成及通过抑制 MMP-9的活性从而减轻哮喘的气道炎症及气道重塑。%ABSTRACT:Objective To investigate the effect of doxycycline on airway inflammation and remodeling in asthmatic rats.Methods Thirty-three male Sprague Dawley rats were randomly divided into three groups:control group,asthma group and doxycycline intervention group.Total cell number and different cell number in BALF were counted.The concentrations of serum IL-5,IL-13 were assayed by ELISA,and the concentration of serum TNF-αwas determined by radioimmunoassay.The expression of MMP-9 and α-SMA in lung tissues were observed by immunohistochemistry.Lung tissues were sliced and stained with HE.These parameters such as bronchial basement membrane perimeter (Pbm),total bronchial wall area (WAt)and smooth muscle area (WAm),which reflected the thickness of airway wall,were measured by image analysis system.Results The count of total cells and eosinophils significantly increased in asthma group and doxycycline intervention group than in control group(P <0.05),and the count of total cells and eosinophils significantly decreased in doxycycline intervention group than in asthma group (P <0.05).The thickness of bronchial wall and smooth muscle layer were significantly thicker in asthma group and doxycycline intervention group than in normal group (P < 0.05 ),and the thickness of bronchial wall and smooth muscle layer were significantly thinner in doxycycline intervention group than in asthma group (P < 0.05 ).The concentrations of serum IL-5,IL-13 and TNF-α were significantly higher in asthma group (38.63 ± 6.64)ng/L and doxycycline intervention group (20.42±4.50)ng/L than in control group (1 5.92 ±3.66)ng/L(P <0.05),and the concentrations of serum IL-5,IL-13 and TNF-α were significantly lower in doxycycline intervention group than in asthma group (P < 0.05 ).The average optical density of MMP-9 and α-SMA of asthma group (0.52 ± 0.06 )and doxycycline intervention group (0.39±0.06)were significantly higher than those of control group (0.24±0.06)(P <0.05 ),and the average optical density of MMP-9 andα-SMA were significantly lower in doxycycline intervention group than in asthma group(P <0.05).Conclusion Doxycycline can decrease asthmatic airway inflammation by inhibiting the activity of MMP-9 and influencing the production of inflammatory mediators and improve airway remodeling of asthma through inhibiting the activity of MMP-9.