CAJ | 학술논문

目的：研究阿奇霉素对慢性阻塞性肺疾病（简称慢阻肺）模型大鼠的防治作用，从气道炎症及黏液高分泌角度探讨其作用机制。方法：将18只雄性SD大鼠随机分为正常对照组、慢阻肺模型组、阿奇霉素治疗组，每组6只。通过烟熏及大鼠气管内注入脂多糖（ LPS）的方法建立慢性阻塞性肺疾病大鼠模型。 HE染色观察大鼠肺组织病理变化。肺功能仪检测大鼠肺通气功能。 ELISA检测各组大鼠支气管肺泡灌洗液（ BALF）中白细胞介素（IL）－8、IL－17和肿瘤坏死因子－α（TNF－α）的含量。 Western blot及real－time PCR检测支气管肺组织中MUC5ac和Toll样受体4（ TLR4）蛋白及mRNA的表达。结果：模型组大鼠支气管肺组织HE染色结果符合慢阻肺病理改变。与模型组比较，治疗组损伤程度显著减轻。模型组与对照组比较，肺功能明显下降，大鼠BALF中IL－8、IL－17、TNF－α含量明显增高（P＜0．05），肺组织中MUC5ac和TLR4蛋白及mRNA表达水平显著增高（P＜0．05）。与模型组比较，治疗组肺功能的下降减轻，大鼠BALF中IL－8、IL－17、TNF－α含量的升高受到明显抑制（ P ＜0．05），肺组织中MUC5ac和TLR4蛋白及mRNA表达水平的受到明显抑制（ P ＜0．05）。结论：阿奇霉素可降低慢阻肺模型大鼠BALF中IL－8、IL－17和TNF－α水平，抑制肺组织内MUC5ac和TLR4蛋白表达，通过减轻气道炎症及黏液高分泌来达到防治慢阻肺的作用。
목적：연구아기매소대만성조새성폐질병（간칭만조폐）모형대서적방치작용，종기도염증급점액고분비각도탐토기작용궤제。방법：장18지웅성SD대서수궤분위정상대조조、만조폐모형조、아기매소치료조，매조6지。통과연훈급대서기관내주입지다당（ LPS）적방법건립만성조새성폐질병대서모형。 HE염색관찰대서폐조직병리변화。폐공능의검측대서폐통기공능。 ELISA검측각조대서지기관폐포관세액（ BALF）중백세포개소（IL）－8、IL－17화종류배사인자－α（TNF－α）적함량。 Western blot급real－time PCR검측지기관폐조직중MUC5ac화Toll양수체4（ TLR4）단백급mRNA적표체。결과：모형조대서지기관폐조직HE염색결과부합만조폐병리개변。여모형조비교，치료조손상정도현저감경。모형조여대조조비교，폐공능명현하강，대서BALF중IL－8、IL－17、TNF－α함량명현증고（P＜0．05），폐조직중MUC5ac화TLR4단백급mRNA표체수평현저증고（P＜0．05）。여모형조비교，치료조폐공능적하강감경，대서BALF중IL－8、IL－17、TNF－α함량적승고수도명현억제（ P ＜0．05），폐조직중MUC5ac화TLR4단백급mRNA표체수평적수도명현억제（ P ＜0．05）。결론：아기매소가강저만조폐모형대서BALF중IL－8、IL－17화TNF－α수평，억제폐조직내MUC5ac화TLR4단백표체，통과감경기도염증급점액고분비래체도방치만조폐적작용。
[ABSTRACT]AIM:Toobservetheeffectofazithromycinontheratswithchronicobstructivepulmonarydisease ( COPD) , and to explore the underlying mechanism about the airway inflammation and mucus hypersecretion.METH-ODS:Male SD rats were randomly divided into normal control group, COPD model group, azithromycin treatment group. The COPD model was established by the method of cigarette smoking combined with intratracheal injection of LPS.Patho-logical changes of the bronchi and lung tissues of the rats were observed with HE staining.Pulmonary ventilation function in the rats was detected with pulmonary function instrument.The levels of IL-8, IL-17 and TNF-αin bronchoalveolar lavage fluid (BALF) were measured by ELISA.The expression of MUC5ac and TLR4 at mRNA and protein levels in bronchi and lung tissues was determined by real-time PCR and Western blot.RESULTS:HE staining showed that the changes of bron-chi and lung tissues in model group were consistent with typical pathological manifestations of COPD .Compared with model group, these changes were alleviated in treatment group.The pulmonary functions in model group were significantly de-creased compared with control group.The levels of IL-8, IL-17 and TNF-αin the BALF in model group were significantly increased compared with control group (P<0.05).The expression of MUC5ac and TLR4 at mRNA and protein levels in model group was significantly higher than that in control group (P<0.05).Compared with model group, the degree of the descent in pulmonary function in treatment group was significantly lessened.Compared with model group, the levels of IL-8, IL-17 and TNF-αin treatment group were significantly inhibited (P<0.05).Furthermore, the expression of MUC5ac and TLR4 at mRNA and protein levels in treatment group was significantly lower than that in model group ( P<0.05 ) . CONCLUSION:Azithromycin decreases the levels of IL-8, IL-17 and TNF-αin the BALF of COPD model rats, inhibits the protein expression of MUC5ac and TLR4 in the lung tissues, thus playing a preventive and therapeutic role to reduce airway inflammation and airway mucus hypersecretion.