阿奇霉素对哮喘大鼠气道重塑的影响

目的探讨阿奇霉素对哮喘大鼠气道重塑的影响及其作用机制。方法将32只Sprauge-Dawley大鼠随机分为空白对照组(C组)、哮喘模型组(M组)、阿奇霉素组(A组)、地塞米松组(D组),每组8只,各组动物于末次雾化激发后24 h内处死,留取右肺组织制成病理切片,行组织病理学检查观察肺组织病理学改变;医学图像分析系统测量气道重塑参数;免疫组织化学技术检测肺组织转化生长因子-β1(TGF-β1)、基质金属蛋白酶-9(MMP-9)、血管内皮生长因子(VEGF)在肺组织中的表达情况。结果与C组相比,M组支气管、血管周围见大量炎性细胞浸润,气道壁增厚,胶原沉积增加,黏液分泌增多,A组和D组上述改变明显减轻;A组、D组总管壁厚度、平滑肌厚度较C组增高(P<0.01),较M组明显降低(P<0.01);A组、D组大鼠肺组织TGF-β1、MMP-9、VEGF表达水平较C组升高(P<0.01),较M组降低(P<0.01);大鼠气道平滑肌厚度与肺组织中TGF-β1、MMP-9、VEGF的表达水平呈正相关(P<0.01),肺组织中TGF-β1、MMP-9、VEGF表达水平两两相关(P<0.01)。结论阿奇霉素可改善哮喘大鼠气道重塑程度,其机制可能与下调TGF-β1、MMP-9、VEGF表达有关。

Effect of azithromycin on airway remodeling of asthmatic rats

Objective To explore the effect of azithromycin on airway remodeling of asthmatic rats and its possible mechanism.Methods Thirty-two Sprauge-Dawley(SD) rats were divided randomly into normal control group(group C),asthma model group(group M),azithromycin treatment group(group A),and dexamethasone treatment group(group D),eight rats in each group.Twenty-four hours after the final atomization challenge,the rats in each group were executed and the right lung tissues of the rats were collected and then made into pathological sections.The lung tissue sections were examined by histopathology for pathologic changes.Parameters of airway remodeling were determined by medical image analysis system.The expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase-9(MMP-9),vascular endothelium growth factor(VEGF) in rats lung tissue were observed by immunohistochemistry.Results Compared with the group C,rats in group M demonstrated that inflammatory cells infiltrated around the bronchus and the vascular with airway wall thickness,collagen deposition and the mucus production increased.In group A and group D,the histopathological changes were much lighter than those of group M.The thickness of airway wall and smooth muscle in group A and D increased compared with the group C and decreased compared with the group M(P<0.01).The protein expressions of the TGF-β1,MMP-9,VEGF in group A and D were higher than those of group C(P<0.01) and lower than those of group M(P<0.01).There was a significantly positive correlation between the thickness of smooth muscle and the protein expressions of the TGF-β1,MMP-9,VEGF in lung tissue(P<0.01).And among these three indices,the expression level was pairwise correlation(P<0.01).Conclusion Azithromycin can improve the degree of airway remodeling.Its mechanism maybe relate to down-regulate the expression of the TGF-β1,MMP-9,and VEGF in lung tissue.