小剂量红霉素对香烟烟雾诱导肺气肿中缺氧诱导因子-1α的抑制作用及其机制  

Inhibitory effect of low-dose erythromycin on hypoxia-inducible factor-1α in cigarette smoke-induced emphysema and its mechanism

作　　者：顾冬雪 谷秀[2] 张雪云 GU Dong-xue;GU Xiu;ZHANG Xue-yun(Department of Respiratory Medicine,the People's Hospital of China Medical University,the People's Hospital of Liaoning Province,Shenyang 110016,China;Department of Pulmonary and Critical Care Medicine,Shengjing Hospital of China Medical University,Shenyang 110004,China)

机构地区：[1]中国医科大学人民医院辽宁省人民医院呼吸内一科,辽宁沈阳110016 [2]中国医科大学附属盛京医院呼吸与危重症医学科,辽宁沈阳110004

出　　处：《实用药物与临床》2020年第3期198-202,共5页Practical Pharmacy and Clinical Remedies

基　　金：辽宁省教育厅2019年度科学研究项目(QN2019014);辽宁省自然科学基金计划指导计划(2019-ZD-0766、2018011494-301)。

摘　　要：目的探索小剂量红霉素对慢性阻塞性肺疾病(Chronic obstructive pulmonary disease,COPD)的抗炎作用及其潜在机制。方法将实验大鼠(雄性Wistar大鼠)随机分为3组,每组8只:正常对照组(C组),香烟烟雾模型组(CS组),红霉素+香烟烟雾模型组(ERY+CS组)。通过香烟烟雾诱导制备大鼠肺气肿模型,同时通过灌胃给予大鼠小剂量红霉素治疗。对比三组肺病理组织形态学改变,肺功能,肺泡灌洗液(BALF)中炎症介质(TNF-α及IL-8)表达以及肺组织缺氧诱导因子-1α(HIF-1α)的表达。结果与C组相比,CS组肺平均内衬间隔(MLI)及平均肺泡数(MAN)均明显增加(P<0.05);与CS组相比,ERY+CS组MLI及MAN均明显好转(P<0.05)。与C组相比,CS组大鼠BALF中炎症介质TNF-α及IL-8表达均明显增高(P<0.01)。经红霉素干预后,ERY+CS组TNF-α及IL-8表达有所降低(P<0.01);香烟烟雾暴露后,CS组大鼠肺功能呈现明显的阻塞性通气功能障碍,FEV0.3及FEV0.3/FVC均降低(P<0.01)。经红霉素干预治疗后,ERY+CS组大鼠肺功能明显改善(P<0.01);免疫组化及Western blot结果表明,香烟烟雾诱导后,CS组大鼠肺气肿组织HIF-α蛋白表达均明显增高(P<0.01);红霉素干预后,ERY+CS组香烟烟雾诱导的HIF-α增高较前降低(P<0.05)。结论小剂量红霉素可通过调控抑制肺部HIF-1α的表达,从而发挥对香烟烟雾诱导的肺气肿的保护性作用,进而改善患者的肺部炎症反应,改善肺功能。Objective To explore the anti-inflammatory effect of low-dose erythromycin on chronic obstructive pulmonary disease(COPD)and its underlying mechanism.Methods The rats were subdivided into the following groups randomly:control group(group C),cigarette smoke model group(group CS)and erythromycin+cigarette smoke model(ERY+CS group).A model of rat emphysema was prepared by cigarette smoke induction,and a small dose of erythromycin was administered to the rats by intragastric administration.The morphological changes of lung pathology,lung function,expression of inflammatory mediators(TNF-αand IL-8)in lung alveolar lavage fluid(BALF)and expression of hypoxia-inducible factor-1α(HIF-1α)in lung tissue were compared.Results Compared with group C,the mean lung lining interval(MLI)and mean alveolar number(MAN)were significantly increased in group CS(P<0.05).Compared with group CS,the MLI and MAN in ERY+CS group were significantly improved(P<0.05).Compared with group C,the expression of TNF-αand IL-8 in the BALF of group CS was significantly increased(P<0.01).The expression of TNF-αand IL-8 in ERY+CS group after erythromycin intervention was decreased(P<0.01)compared with group C.After exposure to cigarette smoke,the lung function test of group CS showed obvious obstructive ventilatory dysfunction with decreased FEV0.3 and decreased FEV0.3/FVC(P<0.01).After erythromycin treatment,the lung function of ERY+CS group was significantly improved(P<0.01).The results of immunohistochemistry and Western blot showed that the expression of HIF-αprotein increased significantly after erythromycin treatment in group CS(P<0.01),but it decreased after erythromycin intervention in ERY+CS group(P<0.05).Conclusion Low-dose erythromycin can inhibit the expression of HIF-1αin the lungs,thereby exerting a protective effect on cigarette smoke-induced emphysema,and improving lung inflammation and lung function.

关 键 词：慢性阻塞性肺疾病 缺氧诱导因子-1Α 红霉素 肺气肿 

分 类 号：R563.3[医药卫生—呼吸系统]