阿奇霉素对哮喘模型小鼠气道上皮细胞基质金属蛋白酶-9表达及气道重塑指标的影响研究

Effects of Azithromycin on the Expression of Matrix Metalloproteinase-9 of Airway Epithelial Cell in Asthmatic Mice and Airway Remodeling Indicator

目的:观察阿奇霉素对哮喘模型小鼠气道上皮细胞基质金属蛋白酶-9(MMP-9)表达及气道重塑指标的影响,探讨其在哮喘预防中的作用。方法:取小鼠随机分为正常对照组(生理盐水)、模型组(生理盐水)、阳性对照组(地塞米松,0.18mg·mL-1)和阿奇霉素低、中、高剂量组(0.2、0.4、0.8mg·mL-1),每组10只,除正常对照组外其余各组腹腔注射卵蛋白致敏并雾化卵蛋白激发15d建立哮喘模型,每日雾化前1h腹腔注射相应药物0.5mL,末次激发24h后,观察各组小鼠肺组织病理学变化,检测气道上皮细胞MMP-9表达及气道重塑指标。结果:与正常对照组比较,模型组小鼠气道平滑肌明显增厚,上皮细胞脱落,炎性细胞浸润增多;而阿奇霉素各剂量组和阳性对照组上述病变较模型组均有减轻。与模型组比较,阳性对照组和阿奇霉素各剂量组小鼠MMP-9表达(P<0.05)及气道重塑指标(3种面积(支气管总管壁面积、气道内壁面积、平滑肌面积)与基底膜周径之比)均明显下降(P<0.01),但仍高于正常对照组(P<0.01)。结论:阿奇霉素可能通过下调MMP-9表达延缓气道重塑的病理变化,从而减慢哮喘气道重塑的进程。

OBJECTIVE： To investigate the effects of azithromycin on the expression of matrix metalloproteinase-9 （MMP-9） of airway epithelial cell and airway remodeling indicator, and to evaluate the effect of it on the prevention of asthma. METHODS： Mice were randomly divided into normal control group （normal saline）, model group （normal saline）, positive control group （dexamethasone, 0.18 mg.mL-1） and azithromycin low-dose, medium-dose and high-dose groups （0.2, 0.4, 0.8 mg.mL-1） with 10 mice in each group. Those groups were sensitized with intraperitoneal injection of ovalbumin （OA）, followed by aerosolized OA to challenge them for 15 days to establish asthma model except for normal control group. And they were intraperitoneally inject- ed with relevant drugs 0.5 mL 1 hour before aerosol inhalation. 24 hours after the last challenge, the pathological changes of lung tissue were observed and the expression of MMP-9 in bronchial epithelium and airway remodeling indicator were determined. RE- SULTS： Compared with normal control group, HE staining showed thickening smooth muscle, shedding epithelial cells and increas- ing infiltration of inflammatory cells in model group. Those pathological changes of azithromycin groups and positive control group relieved, compared with model group. The expression of MMP-9 （P〈0.05） and remodeling index （ratio of 3 kinds of areas （total area of bronchial wall, inner airway area, smooth muscle layer area） to basement membrane circumference） were decreased signifi- cantly （P〈0.01） in positive control group and azithromycin groups, compared with model group, but were still higher than normal control group （P〈0.01）. CONCLUSION： Azithromycin can reduce the expression of MMP-9 and delay the pathological change of airway remodeling so as to slow down the process of airway remodeling.