香烟烟雾提取物影响肺泡上皮细胞谷胱甘肽和γ谷氨酰半胱氨酸合成酶的表达

香烟中含有大量的氧化剂，吸烟可导致肺内氧化/抗氧化失衡，并最终导致慢性阻塞性肺疾病(COPD)。谷胱甘肽(GSH)是肺内一种重要的抗氧化剂，在氧化剂介导的肺部炎症和肺损伤中起着重要的防御作用。本组研究系统观察香烟烟雾提取物(CSC)对大鼠肺泡上皮细胞(CCIA49)GSH及其合成限速酶γ谷氨酰半胱氨酸合成酶(γ-GCS)表达的影响，旨在深入探讨吸烟引起慢性气道炎症的机制。     

白介素17、白介素6在香烟烟雾诱导大鼠气道炎症模型中的变化

目的 观察香烟烟雾暴露大鼠气道炎症模型血清和支气管肺泡灌洗液(BALF)中白介素17(IL-17)、IL-6的变化,以探讨其可能在气道炎症中所起的作用.方法 40只健康清洁级雄性Wistar大鼠随机分为四组:12周正常对照组(C1组)、24周正常对照组(C2组)、12周香烟烟雾暴露组(S1组)、24周香烟烟雾暴露组(S...     

SB203580对烟雾暴露的哮喘大鼠的影响

目的建立烟雾暴露的支气管哮喘(简称哮喘)大鼠模型,观察p38有丝分裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)抑制剂SB203580对其的治疗作用。方法将Wistar大鼠随机分为4组,即正常对照组、哮喘组、烟雾暴露的哮喘组及SB203580干预组。动物肺功能仪测定大鼠呼气阻力、吸气阻力及肺顺应性,观察肺组织病理学改变,通过ELISA检测大鼠肺组织中IL-4、IL-5和IL-8的表达。结果与烟雾暴露的哮喘组相比,SB203580干预组大鼠的气道阻力显著下降,肺顺应性显著升高,差异有统计学意义(P<0.05);气道炎症明显减轻;肺组织中IL-4、IL-5和IL-8的含量显著下降,差异有统计学意义(P<0.05)。结论 p38 MAPK抑制剂SB203580可以改善烟雾暴露的哮喘大鼠的气道炎症,减轻其支气管收缩反应。     

SB203580对烟雾暴露的哮喘大鼠的影响

目的 建立烟雾暴露的支气管哮喘(简称哮喘)大鼠模型,观察p38有丝分裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)抑制剂SB203580对其的治疗作用.方法 将Wistar大鼠随机分为4组,即正常对照组、哮喘组、烟雾暴露的哮喘组及SB203580干预组.动物肺功能仪测定大鼠呼气阻力、吸气阻力及肺顺应性,观察肺组织病理学改变,通过ELISA检测大鼠肺组织中IL-4、IL-5和IL-8的表达.结果 与烟雾暴露的哮喘组相比,SB203580干预组大鼠的气道阻力显著下降,肺顺应性显著升高,差异有统计学意义(P＜0.05);气道炎症明显减轻;肺组织中IL-4、IL-5和IL-8的含量显著下降,差异有统计学意义(P ＜0.05).结论 p38 MAPK抑制剂SB203580可以改善烟雾暴露的哮喘大鼠的气道炎症,减轻其支气管收缩反应.     

熏烟对小鼠肺内Muc1表达的影响及机制

目的 观察熏烟对小鼠肺组织中Muc1表达的影响,并初步探讨其表达水平的改变与烟雾刺激的关系.方法 C57雄性小鼠随机分为熏烟组(8只)和对照组(8只),熏烟处理或正常饲养相同时间后处死小鼠,对支气管肺泡灌洗液(BALF)进行细胞计数、染色和分类,同时测定BALF中肿瘤坏死因子α(TNF-α)水平;通过酶联免疫吸附测定法及蛋白质免疫印迹法对BALF及肺组织中Muc1蛋白水平进行检测.同时对香烟烟雾提取物刺激肺上皮来源的A549细胞后MUC1的表达水平进行了验证.结果 与对照组比较,熏烟组小鼠肺组织中出现明显炎症细胞浸润,BALF中的细胞总数、中性粒细胞数、巨噬细胞数均增高.同时,熏烟组小鼠的肺组织及BALF中的Muc1表达水平以及BALF中TNF-α的水平均高于对照组(P＜0.05或P＜0.01).此外,香烟烟雾提取物刺激A549细胞后,可诱导黏蛋白MUC1表达上升.结论 熏烟可以导致小鼠肺组织炎症反应并伴随Muc1的表达水平升高和TNF-α 分泌的增加,MUC1表达水平的增加可能与香烟烟雾直接作用于肺上皮细胞有关.     

烟草烟雾诱导的慢性阻塞性肺疾病模型大鼠消化道的病理特点

目的观察慢性阻塞性肺疾病(COPD)模型大鼠消化道的病理改变,为探究COPD营养不良的机制提供理论依据。方法采用单纯烟草烟雾暴露的方法建立COPD大鼠模型。造模结束后,检查大鼠肺功能、动脉血气、支气管肺泡灌洗液炎症细胞和炎症介质水平以及肺组织、肝、脾、胃、小肠的病理变化。结果与正常对照组大鼠相比,模型组大鼠体质量明显减轻;功能残气量、肺总量上升,静态肺顺应性增加,呼气流速50毫秒用力呼气量/用力肺活量比值下降;肺泡结构大小不一、部分肺泡间隔断裂、融合;支气管肺泡灌洗液中,炎症细胞总数及分类计数(中性粒细胞、巨噬细胞及淋巴细胞)均高于对照组,促炎介质白细胞介素-6(IL-6)和单核细胞趋化蛋白1水平高于对照组,而抗炎介质IL-10低于对照组;肝小叶中央静脉充血伴炎症细胞浸润,肝细胞轻度水肿、脾出现淤血、胃出现轻度糜烂、小肠黏膜萎缩伴炎症细胞浸润。结论在COPD大鼠模型中,肝、脾、胃黏膜、小肠黏膜等消化道组织均出现充血、水肿、淤血、糜烂、炎症细胞浸润等炎症性病理改变,这些病变可能与COPD营养不良有关。     

香烟烟雾刺激诱导肺动脉高压动物模型的构建

目的探讨利用单纯香烟烟雾刺激造模能否有效构建肺动脉高压疾病模型。方法把20只清洁级SD大鼠,随机分为对照组(9只)、肺动脉高压(模型)组(11只),用香烟烟雾刺激的方法诱导肺动脉高压模型。在造模满4个月时检测各组大鼠血流动力学指标,取肺组织制作病理切片,比较两组大鼠的肺血管重构程度。结果与对照组相比,模型组右室收缩压较对照组显著增大,表明造模成功。模型组右室肥厚程度也显著加重。与对照组相比,模型组肺血管重塑的水平也更为严重。结论单纯香烟烟雾刺激的方法能有效建立肺动脉高压动物模型,在这一过程中肺动脉高压的发生、发展可能与肺血管重塑及右心室肥厚有关。     

单纯烟雾暴露建立慢性阻塞性肺疾病大鼠模型的方法学研究

目的探讨单纯烟雾暴露建立慢性阻塞性肺疾病(COPD)大鼠模型的方法,为COPD动物模型的建立提供参考。方法将24只Wistar大鼠随机分为对照组、烟雾暴露8周组、烟雾暴露10周组、烟雾暴露12组,每组6只。将烟雾暴露组大鼠置于自制玻璃染毒箱中,烟雾暴露2 h/d,5 d/周;对照组大鼠同时放在另一自制玻璃染毒箱中,自由呼吸空气。观察各组大鼠一般情况,比较各组大鼠肺功能指标、支气管肺泡灌洗液炎性细胞计数及肺组织病理学检查结果。结果 (1)一般情况:对照组大鼠整个实验过程中活动正常,毛发白亮细密,精神佳,无气促、发绀,食量好;烟雾暴露8周组大鼠活动减少,倦卧,毛发黄涩无光泽;烟雾暴露10周组大鼠活动进一步减少,精神不佳,毛发黄涩,食欲下降,间歇咳嗽偶有喘息;烟雾暴露12周组大鼠活动较烟雾暴露8周组、烟雾暴露10周组大鼠减少,精神萎靡,毛发枯糙发黄脱落,口唇及指抓发绀,消瘦。(2)肺功能指标:烟雾烟雾暴露12周组大鼠0.3秒用力呼气容积与用力肺活量比值(FEV0.3/FVC)和肺动态顺应性(Cdyn)低于对照组、烟雾暴露8周组、烟雾暴露10周组,吸气阻力(Ri)和呼气阻力(Re)高于对照组、烟雾暴露8周组、烟雾暴露10周组(P0.05);烟雾暴露8周组和烟雾暴露10周组大鼠Cdyn低于对照组(P0.05)。(3)支气管肺泡灌洗液炎性细胞计数结果:烟雾暴露8周组、烟雾暴露10周组、烟雾暴露12周组大鼠炎性细胞计数和中性粒细胞分数高于对照组,巨噬细胞分数低于对照组(P0.05);但4组大鼠淋巴细胞分数比较,差异无统计学意义(P0.05)。(4)肺组织病理学检查结果显示,对照组大鼠支气管和肺泡结构清晰,气道黏膜上皮细胞排列整齐,肺泡大小均匀;烟雾暴露8周组大鼠肺组织以炎性细胞浸润为主;烟雾暴露10周组大鼠肺组织炎性细胞浸润更明显,气管壁平滑肌、纤维结缔组织增生,可见少许肺泡壁破坏;烟雾暴露12周组大鼠气道上皮脱落,气道内黏液和细胞阻塞,肺组织结构破坏明显,肺泡扩张,肺泡间隔断裂,相邻肺泡融合形成肺大泡,小血管壁增厚。结论在自制玻璃染毒箱中单纯烟雾暴露12周可成功建立COPD大鼠模型。     

苏子降气汤增强沙美特罗替卡松粉吸入剂对慢性阻塞性肺疾病大鼠抗炎作用的研究

目的探讨苏子降气汤增强沙美特罗替卡松粉吸入剂(ICS/LABA)治疗慢性阻塞性肺疾病(简称慢阻肺)抗炎作用的效果和机制。方法将SD大鼠随机分为对照组、模型组、ICS/LABA组(183 ug/kg)、ICS/LABA+苏子降气汤高、中、低组(3.4 g/kg、1.7 g/kg和0.85 g/kg)。模型大鼠均采用脂多糖加香烟烟雾刺激复制慢阻肺大鼠动物模型。采用酶联免疫吸附法(ELISA)检测血清中白介素-8(IL-8)、肿瘤坏死因子α(TNF-α)和肺泡灌洗液中转化生长因子β1(TGF-β1)的浓度,观察肺组织病理变化,免疫组化检测肺组织中TNF-α的表达,实时荧光定量聚合酶链式反应(RT-PCR)检测肺组织中TNF-αmRNA的表达。结果苏子降气汤与沙美特罗替卡松粉吸入剂联用能降低IL-8、TNF-α和TGF-β1含量,其中高、中剂量效果更加显著(P0.01,P0.05);病理学结果显示高、中剂量组肺组织炎症反应明显改善;免疫组化检测显示高、中剂量组肺组织中TNF-α明显下降;高、中剂量组肺组织中TNF-αmRNA相对表达量明显降低(P0.01,P0.05)。结论苏子降气汤与沙美特罗替卡松粉吸入剂联合使用对慢阻肺大鼠具有明显疗效,可能是通过降低TNF-α的表达,增强沙美特罗替卡松粉吸入剂的抗炎作用。     

熊果酸对慢性阻塞性肺疾病的保护作用研究

目的探讨熊果酸对慢性阻塞性肺疾病大鼠的作用及潜在作用机制。方法 30只雄性SD大鼠随机均分为对照组,慢阻肺模型组和熊果酸组。通过烟雾暴露联合气道滴入脂多糖构建大鼠慢阻肺模型。熊果酸组烟雾暴露前30 min给予熊果酸(40mg/kg)灌胃,对照组和模型组给予等量生理盐水灌胃,共30天。处死大鼠前观察大鼠一般情况,行肺功能测定和收集支气管肺泡灌洗液行细胞分类计数,处死后收集肺脏和血清。HE染色检测肺组织病理形态;酶联免疫法和逆转录聚合酶链式反应检测血清,BALF和肺组织中白介素-6(IL-6),白介素1β(IL-1β)和肿瘤坏死因子-ɑ(TNF-α)表达水平;Western blotting检测肺组织Toll样受体4,髓样分化因子88(My D88),p65和p65表达水平。结果与模型组相比,熊果酸预处理可明显减轻肺组织病理损害,改善大鼠肺功能和一般情况,减少TLR4,My D88,p-p65、IL-6、IL-1β和TNF-α的表达水平,降低肺泡灌洗液中中性粒细胞总数和中性粒细胞比。结论熊果酸可通过抑制炎症减轻慢性阻塞性肺疾病大鼠肺功能的恶化,其作用机制与抑制TLR-4/NF-KB信号通路激活相关。     

香烟烟雾暴露对支气管哮喘大鼠OX-62、白介素12表达的影响

目的 研究香烟烟雾暴露对支气管哮喘(简称哮喘)大鼠肺组织树突状细胞(dendritic cell,DC)的特异性标记蛋白OX-62、血浆及支气管肺泡灌洗液(BALF)白介素12(IL-12)表达的影响,探讨吸烟加重哮喘的免疫学机制.方法 30只雄性Wistar大鼠随机分为对照组、哮喘组、暴露组;建立哮喘大鼠模型和哮喘大...     

A study on tumor necrosis factor alpha, macrophage inflammatory protein-2 and myeloperoxidase in blood, broncho-alveolar fluid and lung tissues of rat chronic bronchitis model

OBJECTIVE: To study the nature and mechanisms of airway inflammation in chronic bronchitis and observe the effects of inhaled glucocorticoids on inflammatory indices. METHODS: Rat chronic bronchitis model was established by intratracheal instillation of small dose of lipopolysaccharide (LPS, 1 g/L). Experiments were performed in 28 male Sprague-Dawley rats, which comprised four groups in random, i.e. chronic bronchitis model group, normal saline treated group, dexamethasone treated group and healthy control group. The levels of myeloperoxidase (MPO) of blood and lung tissues, and tumor necrosis factor (TNF)alpha and macrophage inflammatory protein-2 (MIP-2) of plasma, broncho-alveolar fluid (BALF) and lung tissues were determined by biochemical and ELISA methods. Total and differential white blood cell counts of BALFwere carried out. RESULTS: (1) The levels of TNFalpha and MIP-2 in BALF and lung tissues, and MPO in lung tissues of chronic bronchitis model group were significantly increased than those of control group (P < 0.05). (2) More significant increase in total white blood cell count and neutrophils in BALF was found in rat chronic bronchitis group than in control group (P < 0.001). (3) Significant positive correlations were observed between the level of MPO and MIP-2 of lung tissues, the level of MPO and TNFalpha of lung tissue and the total cell counts and the level of MIP-2 of BALF and lung tissue. (4) More significant decrease in total cell counts and neutrophils of BALF and levels of MPO in lung tissue was found in dexamethasone-treated group as compared to those of chronic bronchitis group. CONCLUSION: Recruitment and activation of neutrophils seem to be the characteristics of chronic bronchitis. TNFalpha and MIP-2 may be involved in the process of chemotaxis and activation in airway inflammation in chronic bronchitis. Inhaled steroids might have some effects on chronic bronchitis by limiting the airway inflammation.     

Prenatal cigarette smoke decreases lung cAMP and increases airway hyperresponsiveness

Epidemiologic studies suggest that in utero exposure to tobacco smoke, primarily through maternal smoking, increases the risk for asthma in children; however, the mechanism of this phenomenon is not clear. Cyclic adenosine monophosphate relaxes airway smooth muscles in the lung and acts as an antiasthmatic. In this study, we examined the effects of in utero cigarette smoke exposure of Balb/c mice on airway responsiveness, as determined by Penh measurements. Animals exposed prenatally but not postnatally to cigarette smoke exhibited increased airway hyperresponsiveness after a single intratracheal injection of Aspergillus fumigatus extract. The increased airway hyperresponsiveness was not associated with increased leukocyte migration or mucous production in the lung but was causally related to decreased lung cyclic adenosine monophosphate levels, increased phosphodiesterase-4 enzymatic activity, and phosphodiesterase-4D (PDE4D) isoform-specific messenger ribonucleic acid expression in the lung. Exposure of adult mice to cigarette smoke did not significantly alter airway responsiveness, cyclic adenosine monophosphate levels, or the phosphodiesterase activity. These results suggest that prenatal exposure to cigarette smoke affects lung airway reactivity by modulating the lung cyclic adenosine monophosphate levels through changes in phosphodiesterase-4D activity, and these effects are independent of significant mucous production or leukocyte recruitment into the lung.     

白介素17在慢性阻塞性肺疾病大鼠肺组织中的表达及与气道炎症及重塑的关系

目的 探讨白介素17(IL-17)在慢性阻塞性肺疾病(COPD)大鼠气道炎症及重塑中的作用.方法 采用被动吸烟80 d来制备大鼠COPD模型.支气管肺泡灌洗计数支气管肺泡灌洗液(BALF)中细胞计数和百分比;采用半定量图像分析法测量小气道管壁和平滑肌层厚度;免疫组织化学法检测肺组织IL-17的表达;酶联免疫吸附试验法检...     

烟草雾吸入导致慢阻肺机制的实验研究：大鼠Clara细胞结构 …

为探讨烟草雾吸入诱导的慢性阻塞性肺疾病（ＣＯＰＤ）大鼠气道Ｃｌａｒａ细胞及其分泌蛋白（又称Ｃｌａｒａ细胞１０ｋＤａ蛋白，ＣＣ１０）表达的变化，采用自制的染毒箱，使大鼠吸入烟草雾制作ＣＯＰＤ模型，对Ｃｌａｒａ细胞进行电镜及免疫组化观察，并测定大鼠气道阻力及呼吸系统总顺应性。ＣＯＰＤ大鼠终末及呼吸性细支气管Ｃｌａｒａ细胞数量减少，胞浆内滑面内质网扩张；终末及呼吸性细支气管上皮细胞ＣＣ１０表达减少；呼吸     

烟草雾吸入导致慢阻肺机制的实验研究——大鼠Clara细胞结构及其分泌蛋白的变化

为探讨烟草雾吸入诱导的慢性阻塞性肺疾病 (COPD)大鼠气道Clara细胞及其分泌蛋白 (又称Clara细胞 10kDa蛋白 ,CC10 )表达的变化 ,采用自制的染毒箱 ,使大鼠吸入烟草雾制作COPD模型 ,对Clara细胞进行电镜及免疫组化观察 ,并测定大鼠气道阻力及呼吸系统总顺应性。COPD大鼠终末及呼吸性细支气管Clara细胞数量减少 ,胞浆内滑面内质网扩张 ;终末及呼吸性细支气管上皮细胞CC10表达减少 ;呼吸功能检查显示气道阻力增加、呼吸系统总顺应性下降 ;气道上皮细胞CC10阳性细胞百分率与气道阻力呈负相关。COPD大鼠终末及呼吸性细支气管上皮细胞Clara细胞数量减少 ,气道上皮细胞CC10表达减少 ,CC10阳性细胞百分率与气道阻力呈负相关、与动态顺应性呈正相关。这可能与大鼠气道阻力增加及呼吸系统总顺应性下降有关     

The relation between peripheral blood leukocyte counts and respiratory symptoms, atopy, lung function, and airway responsiveness in adults

STUDY OBJECTIVES: Eosinophils and neutrophils play major roles, respectively, in the pathogenesis of asthma and COPD, and it is well recognized that levels of these cells in peripheral blood are increased in relation to their pulmonary involvement. However, the relation between peripheral blood cell counts of the other major leukocyte groups and these lung diseases or markers of allergy or airflow obstruction is less clear. We have therefore investigated the association between peripheral blood levels of eosinophils, neutrophils, basophils, monocytes, and lymphocytes and the occurrence of chronic respiratory symptoms, atopy, lung function, and bronchial hyperresponsiveness, and the modifying effect of age, in adults. DESIGN: A cross-sectional general population study. SETTING: Data on > 2,000 British adults, who originally participated in a study of diet and lung health, were analyzed using multiple linear and logistic regression to adjust for potential confounders, including age, sex, and smoking history. RESULTS: We found that, like eosinophils, the peripheral basophil count was increased in relation to asthma and associated symptoms, and to airway hyperreactivity and increased total IgE, but differed from eosinophils in that basophils were unrelated to atopy. Monocytes were predominantly associated with symptoms indicative of obstructive airway disease, in similar relation to neutrophils, but both of these leukocyte counts were also increased in asthma patients in older age groups. Lymphocyte counts were unrelated to any objective or subjective marker of disease. CONCLUSIONS: If peripheral blood cell counts reflect pulmonary involvement of these leukocyte groups, basophils and monocytes may play a distinct role in the pathogenesis of allergic and nonallergic respiratory disease.     

Persistent airway obstruction after virus infection is not associated with airway inflammation

BACKGROUND: This study examined the contribution of airway inflammation to the delayed lung function recovery that occurs in some people following virus-induced asthma exacerbations. METHODS: Subjects (n = 40) were recruited at hospital admission for acute asthma exacerbation. Respiratory virus infection was diagnosed by viral nucleic acid detection and/or cell culture, using induced sputum, nasal, or throat swabs. Data collected included lung function, answers to common cold and asthma control questionnaires, and induced sputum cellular profiles. Subjects were reexamined 4 to 6 weeks postexacerbation and were compared with stable asthmatic subjects (n = 26) who had been recruited from ambulatory care clinics. RESULTS: Persistent airway obstruction, defined as lung function improvement at follow-up (ie, change in FEV1 percent predicted [Delta%FEV1]) of <15%, was observed in 10 subjects (25%). Airway recovery (Delta%FEV1, > or = 15%) was observed in the remaining subjects (30 subjects; 75%). During the acute episode, the airway-recovery group had increased total cell count (p = 0.019), increased number of neutrophils (p = 0.005), and increased percentage of neutrophils (p = 0.0043) compared to the group of stable subjects with asthma. Postexacerbation, the airway-recovery group had reduced numbers of neutrophils and an increased percentage of eosinophils. In contrast, during exacerbation, subjects with persistent airway obstruction showed no differences in inflammatory cell counts compared to stable subjects with asthma, nor did cell counts change postexacerbation. Symptoms improved in both groups postexacerbation. However, in the persistent-airway-obstruction group, asthma remained uncontrolled. CONCLUSION: Persistent airway obstruction and uncontrolled asthma are observed in some people after viral asthma exacerbations. These abnormalities are not associated with inflammatory cell influx into the airway lining fluid during the exacerbation and may reflect the involvement of noncellular elements. Further work should explore other mechanisms leading to incomplete airway recovery.     

Clarithromycin might attenuate the airway inflammation of smoke-exposed asthmatic mice via affecting HDAC2

Background

Smoke has been proved to be one of the most dangerous ingredients leading to the unsatisfying treatment response of asthmatics to inhaled corticosteroids (ICS) therapy. Macrolides, a class of antibiotics, possess the traits of immunomodulation and anti-inflammation besides antimicrobial activity. Given that studies on the efficacy of macrolides on the refractory asthma patient have diverting conclusions, this article was carried on to investigate the effects of macrolide on the airway inflammation of smoke-exposed asthmatic mice.

Methods

BALB/c mice were chosen to be the subjects of this study. They were raised to establish asthma model (OVA group); and one asthma group were exposed to the smoke (SEA group), one asthma group were treat with clarithromycin (CAM group) after smoke exposure. Control group mice were used as parallel comparison. Total inspiratory resistance (RL), expiratory resistance of the lung (Re) and lung compliance (Cdyn) were the main index to evaluate airway hyperresponsiveness (AHR). The histopathological change was studied to assess lung tissue inflammation. Cell counts in bronchoalveolar lavage fluid (BALF) were also tested to represent airway inflammation. IL-4 and CXCL1 in BALF and serum were also used to evaluate the airway inflammation. Histone deacelytase2 (HDAC2) activity of lung tissues was measure by assay kit. HDAC2 expression in the lung tissue had been detected by western blot.

Results

Re, RL and Cdyn were monitored to represent airway responsiveness. All of the three indicators in SEA group were significantly different from control group, while clarithromycin improved airway responsiveness and the three indicator were statistically significant (P<0.01). Histopathology observation had showed massive infiltration of inflammatory cells in both OVA group and SEA group, while inflammation infiltration attenuated in CAM group. Total cell counts in SEA group was much higher than that in CAM group (P=0.019), so were neutrophils (P=0.022) and eosinophils (P=0.042); while macrophages in SEA group decreased when compared to CAM group (P=0.026), IL-4 and CXCL1 level in CAM group were significantly decreased in comparison to those in SEA group (P=0.031, P=0.017). HDAC2 activity in SEA group decreased significantly when compared to control group (P=0.010); while HDAC2 activity in CAM group was improved and significantly better than that in SEA group (P=0.038). The expression of HADC2 in CAM group improved significantly when compared to that in SEA group (P=0.022).

Conclusions

Clarithromycin could improve AHR and attenuate airway inflammation in smoke exposed asthmatic mice which may involve HDAC2. Macrolides might have the potential to serve as the adjunctive treatment to some refractory asthmatics who are smokers or passive smokers.     

香烟烟雾暴露对支气管哮喘大鼠Th1/Th2细胞因子及转录因子GATA-3表达的影响

目的 通过观察香烟烟雾暴露后支气管哮喘(简称哮喘)大鼠Th1/Th2细胞因子及转录因子GATA-3表达的变化.探讨吸烟加重哮喘的免疫学机制.方法 48只雄性Wistar大鼠随机分为对照组、烟雾暴露组、哮喘组、哮喘+烟雾暴露组;建立慢性哮喘大鼠模型和哮喘大鼠香烟烟雾暴露模型,普通病理观察气道壁厚度的变化,酶联免疫吸附试验检测外周血和肺组织γ干扰素(INF-γ)和白介素4(IL-4)含量;免疫印迹检测肺组织GATA-3蛋白表达水平.结果 ①哮喘+烟雾暴露组气道壁厚度[(18.34±0.87)μm 2/μm]较哮喘组[(15.72±0.82)μm 2/μm]和对照组[(8.52±0.58)μm 2/μm]均明显增加,差异有统计学意义(P值均<0.01);②哮喘+烟雾暴露组血浆和肺组织IL-4含量[(34.07±6.11)ng/L]、[(1.41±0.31)ng/L]较哮喘组[(22.57±4.32)ng/L]、[(0.80±0.14)ng/L]和对照组[(11.38±2.90)ng/L]、[(0.27±0.08)ng/L]均增高,差异有统计学意义(P值均<0.05);哮喘+烟雾暴露组血浆INF-γ含量[(9.53±3.28)ng/L]较哮喘组[(58.83±19.57)ng/L]和对照组[(150.87±55.54)ng/L]均降低,差异有统计学意义(P值均<0.05),肺组织INF-γ含量[(0.48±0.10)ng/L]较哮喘组[(0.58±0.23)ng/L]差异无统计学意义;③哮喘+烟雾暴露组GATA-3蛋白表达(1.29±0.08)较哮喘组(0.87±0.04)和对照组(0.45±0.06)均增加,差异有统计学意义(P值均<0.01).结论 香烟烟雾暴露可以通过上调转录因子GATA-3蛋白表达,进而调控Th1/Th2偏移,在哮喘气道炎症及气道重塑的形成中扮演重要角色,为吸烟加重哮喘的免疫学机制之一.