香烟烟雾增加哮喘大鼠肺组织内皮素2的水平及机制

发布时间：2018-04-08 23:16

本文选题：哮喘　切入点：香烟烟雾　出处：《细胞与分子免疫学杂志》2017年08期

【摘要】：目的探讨香烟烟雾对哮喘大鼠肺组织内皮素2(ET-2)表达的影响。方法大鼠腹腔注射鸡卵清蛋白/Al(OH)3混合液1 m L致敏建立哮喘模型(哮喘模型组,n=6),在哮喘模型组基础上烟熏(10支/d)连续4周为香烟烟雾哮喘组(烟雾哮喘组,n=6),分别以地塞米松2 mg/(kg·d)腹腔注射1周、ET受体抑制剂波生坦100 mg/(kg·d)灌胃及联合处理分为地塞米松处理组、波生坦处理组、地塞米松及波生坦处理组,每组6只,设正常对照(正常对照组,腹腔注射生理盐水1 m L,n=6)及香烟烟雾对照[在正常对照组基础上,连续烟熏(10支/d)4周,n=6]。收集左肺上叶支气管肺泡灌洗液(BALF)检测细胞计数及分类,右肺上叶HE染色观察肺组织病理学改变;其余肺组织行Western blot法及免疫组织化学染色法分别检测肺组织c-Jun氨基末端激酶1/2(JNK1/2)、ET-2蛋白水平,硫代巴比妥酸法测丙二醛(MDA)水平,微量酶标法测谷胱甘肽(GSH)水平。结果与对照组比较,香烟烟雾对照组、哮喘模型组、香烟烟雾哮喘组BALF中白细胞数、中性粒细胞数及嗜酸性粒细胞数升高,肺组织中ET-2蛋白、JNK1/2蛋白、MDA及GSH水平升高;而与香烟烟雾哮喘组比较,地塞米松处理组、波生坦处理组、地塞米松及波生坦处理组BALF中白细胞数、中性粒细胞数及嗜酸性粒细胞数均降低。肺组织中ET-2蛋白、JNK1/2蛋白、MDA及GSH表达降低。地塞米松处理组、波生坦处理组、地塞米松及波生坦处理组气道炎症均有改善,地塞米松及波生坦处理组改善最明显。ET-2在地塞米松处理组、波生坦处理组、地塞米松及波生坦处理组肺组织染色强度减少,地塞米松及波生坦处理组染色强度减少更明显。结论香烟烟雾暴露可加重哮喘大鼠气道炎症,ET受体抑制剂波生坦可改善气道炎症,香烟烟雾暴露哮喘发生的炎症机制可能与ET-2及JNK1/2通路有关。
[Abstract]:Objective to investigate the effect of cigarette smoke on the expression of endothelin 2 (et 2) in lung tissue of asthmatic rats.Methods Rats were sensitized by intraperitoneal injection of chicken ovalbumin / AlOHH3 mixture of 1 mL to establish an asthma model (asthma model group, 10 cigarettes / d) for 4 weeks as cigarette smoke asthma group (smog asthma group), the asthma model group was divided into two groups: cigarette smoke asthma group (smoke asthma group) and cigarette smoke asthma group (cigarette smoke asthma group).Dexamethasone (2 mg/(kg d) was intraperitoneally injected with Bosentan (100 mg/(kg d), an et receptor inhibitor, and was divided into dexamethasone treatment group and combined treatment group.BALF was collected from the upper lobe of left lung to detect the cell count and classification, and HE staining was used to observe the histopathological changes of the lung in the upper lobe of the right lung.The other lung tissues were detected by Western blot and immunohistochemical staining for the level of c-Jun aminoterminal kinase 1 / 2, thiobarbituric acid and glutathione glutathione respectively.Results compared with the control group, the number of leukocytes, neutrophils and eosinophils in BALF of cigarette smoke control group, asthma model group and cigarette smoke asthma group were higher than those in control group, while the levels of ET-2 1 / 2 protein and GSH in lung tissue were higher than those in control group.Compared with cigarette smoke asthma group, the number of leukocytes, neutrophils and eosinophils in BALF were decreased in dexamethasone group, Bosentan group, dexamethasone group and Bosentam group.The expression of ET-2 1 / 2 protein and GSH decreased in lung tissue.The airway inflammation was improved in dexamethasone group, Bosentam group, dexamethasone group and Bosentam group. The improvement of ET-2 was most obvious in dexamethasone treatment group and Bosentam treatment group.In dexamethasone and Bosentam groups, the staining intensity of lung tissue was decreased, and that of dexamethasone and Bosentam group was more obvious.Conclusion cigarette smoke exposure can aggravate airway inflammation in asthmatic rats, and Boshentan, an inhibitor of et receptor, can improve airway inflammation. The inflammatory mechanism of cigarette smoke exposure to asthma may be related to the ET-2 and JNK1/2 pathways.
【作者单位】：徐州医科大学附属医院呼吸内科;
【基金】：国家自然科学基金(81600044) 江苏省青年医学人才项目(QNRC2016798)
【分类号】：R562.25

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