雷帕霉素对哮喘大鼠气道重塑和白细胞介素-8白细胞介素-10的影响

Effects of rapamycin on airway remodeling, IL-8 and IL-10 in asthmatic rats

目的观察雷帕霉素对哮喘大鼠模型气道重塑和肺组织白细胞介素(IL)-8、IL-10的影响,探讨其在干预支气管哮喘气道炎症和气道重塑中的作用机制,为临床研究提供实验依据。方法建立哮喘大鼠气道重塑模型,30只SD大鼠按随机数字法随机分为正常对照组(A)、哮喘组(B)、雷帕霉素干预组(C),每组10只。对肺组织切片行苏木素-伊红染色观察气道重塑情况。采用免疫组织化学和图像分析技术的方法测定各组大鼠肺组IL-8、IL-10的表达。结果哮喘组动物出现管壁增厚、平滑肌增生、黏液分泌增加等气道重塑的特征性改变,免疫组织化学染色显示气道各层细胞及炎性细胞均有IL-8表达增多,且IL-10水平也显著减少。雷帕霉素干预组与哮喘组比较,炎症反应轻微,平滑肌增生、黏液分泌不明显,免疫组织化学染色示各细胞IL-8表达也有所降低,IL-10水平表达增高,与正常对照组比较差异有统计学意义(P<0.05)。结论雷帕霉素可减轻哮喘大鼠的气道炎症和气道重塑,并可降低IL-8表达水平,增高IL-10表达水平,调节失衡的致炎因子/抑炎因子比例,发挥对支气管哮喘的炎症抑制和免疫调节作用。

Objective To investigate the effects of rapamycin on airway remodeling and lung tissue IL-8 and IL-10 in asthmatic rats, and to explore the mechanism by which rapamycin intervene in airway inflammation and re-modeling in bronchial asthma, so as to provide experimental basis for clinical research. Methods The asthmatic rat model of airway remodeling was established. Then, 30 SD rats were randomly divided into 3 groups： normal control group, asthma group, and rapamycin intervention group, with 10 rats in each group. Airway remodeling was observed in lung tissue sections with hematoxylin-eosin staining. The IL-8 and IL-10 expressions in lung tissues of each group were measured by immunohistochemistry and image analysis technique. Results The rats in asthma group showed characteristic changes of airway remodeling, such as thickened airway walls, hyperplasia of smooth muscle, and mucus hypersecretion. Immunohistochemical staining showed increased IL-8 expression in structural cells and inflammatory cells in airway layers. The IL-10 level was significantly reduced. Compared with the asthma group, the rapamycin treatment group showed mild inflammatory reaction, less smooth muscle hyperplasia and mucus secretion. Immunohis-tochemical staining showed the lowered IL-8 expression and increased IL-10 expression in all cells, with statistical differences when compared with the control group （P〈0.05）. Conclusion In asthmatic rats, rapamycin can relieve air-way inflammation and remodeling, reduce IL-8 expression, increase IL-10 expression, modulate the imbalance of pro-inflammatory to anti-inflammatory cytokines proportion, and play a role in the anti-inflammation and immune regula-tion in bronchial asthma.