中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

阿奇霉素对慢性阻塞性肺疾病大鼠肺血管重构的影响

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目的探讨阿奇霉素对慢性阻塞性肺疾病(简称慢阻肺)肺血管重构的作用及可能机制。方法将 18 只 SD 大鼠随机分为对照组(A 组)、模型组(B 组)、阿奇霉素干预组(C 组)。B 组与 C 组采用烟熏+气管内注射脂多糖的方法复制慢阻肺大鼠模型,C 组于第 15 d 开始,每日烟熏前 1 h,予以阿奇霉素 50 mg/kg 灌胃,A、B 组予以等量生理盐水灌胃,6 周后处死大鼠。苏木精-伊红染色观察肺组织病理改变,维多利亚蓝+Van Gieson 染色观察肺小动脉形态学改变,ELISA 法检测血清骨桥蛋白(osteopontin,OPN)含量,免疫组化检测 OPN 蛋白表达,荧光定量 PCR 检测 OPN mRNA 的表达。结果与 A 组比较,B、C 组肺血管炎症程度、肺血管重构较明显,C 组肺血管炎症程度和肺血管重构较 B 组轻。B、C 组血清 OPN 含量、肺组织 OPN 蛋白表达、肺组织 OPN mRNA 表达量高于 A 组,C 组血清 OPN 含量、肺组织 OPN 蛋白表达、肺组织 OPN mRNA 表达量较 B 低。血清 OPN 含量、肺组织 OPN 蛋白表达、肺组织 OPN mRNA 表达量与肺血管炎症程度和血管重构成正相关。结论阿奇霉素可减轻慢阻肺大鼠肺血管炎症及肺血管重构,其机制可能与抑制 OPN 的表达有关。

ObjectiveTo investigate the effect of azithromycin on chronic obstructive pulmonary disease (COPD) vascular remodeling and its possible mechanism.MethodsEighteen male SD rats were randomly divided into normal control group (group A), model group (group B) and azithromycin intervention group (group C). In group B and group C, the COPD model was established by passive smoking and intratracheal injection of lipopolysaccharide. On the fifteenth day, group C was intragastricly administrated with azithromycin (50 mg/kg) one hour prior to smoking, while group A and group B were given equal amount of normal saline. All the rats were killed 6 weeks later. Hematoxylin-eosin staining was used to observe lung tissue pathological changes and victoria blue + Van Gieson staining was used to observe the pulmonary artery morphology changes. The serum osteopontin (OPN) was determined with ELISA. The protein expression of OPN was measured with immunohistochemistry and OPN mRNA was detected by RT-PCR.ResultsCompared with group A, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling in groups B and C was more serious, but these changes in group C were lighter than those in group B. The serum OPN content, lung tissue OPN protein and OPN mRNA expression in groups B and C were higher than those in group A, while these parameters in group C were lower than those in group B. The content of serum OPN, the expression of OPN protein and OPN mRNA in lung tissue were positively correlated with the degree of pulmonary vascular inflammation and vascular remodeling.ConclusionAzithromycin can alleviate the pulmonary vascular inflammation and pulmonary vascular remodeling in COPD rats, and its mechanism may be related to inhibiting the expression of OPN.

关键词: 阿奇霉素; 慢性阻塞性肺疾病; 肺血管重构; 骨桥蛋白

Key words: Azithromycin; Chronic obstructive pulmonary disease; Pulmonary vascular remodeling; Osteopontin

引用本文: 樊梅, 邓俊, 王宋平. 阿奇霉素对慢性阻塞性肺疾病大鼠肺血管重构的影响. 中国呼吸与危重监护杂志, 2018, 17(2): 128-133. doi: 10.7507/1671-6205.201710006 复制

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