肥胖型哮喘小鼠体内氧化应激反应变化及其与气道炎症和重构的关系

Oxidative Stress in Airway Inflammation and Remodeling of Obese Mice with Asthma

目的探讨肥胖型哮喘小鼠体内氧化应激反应变化及其与气道炎症和重构的关系。方法 60只雌性C57/6 J小鼠随机分为哮喘组、肥胖组、肥胖哮喘组和对照组。哮喘组在普通饲料基础上,采用卵白蛋白腹腔注射致敏与雾化吸入激发的方法构建哮喘模型;肥胖组采用高脂饮食诱导肥胖模型;肥胖哮喘组在高脂饲料基础上,采用卵白蛋白致敏激发构建肥胖哮喘模型;对照组以普通饲料饲养,生理盐水致敏激发。12周后收集小鼠支气管肺泡灌洗液(BALF)进行细胞计数及分类。ELISA法测定肺组织匀浆中IL-6和8异前列腺素2α(8-iso-PGF2α)水平。肺组织切片观察小鼠病理变化,测定气管壁总面积(WAt)、气道平滑肌面积(WAm)和管腔基底膜周长(Pbm)。结果肥胖哮喘组小鼠BALF中白细胞总数和嗜酸粒细胞比例、肺组织IL-6水平以及气管壁总厚度(WAt/Pbm)均较肥胖组、哮喘组明显增高(P<0.05)。肥胖哮喘组的平滑肌层厚度(WAm/Pbm)较肥胖组增高,但与哮喘组比较差异无统计学意义(P>0.05)。肺匀浆8-iso-PGF2α水平按肥胖哮喘组、哮喘组、肥胖组、对照组的顺序依次降低(P<0.05),且与BALF白细胞总数、WAt/Pbm及IL-6水平呈正相关(r值分别为0.828、0.863和0.891,P<0.01)。结论氧化应激反应参与了肥胖哮喘小鼠气道炎症和重构过程。

Objective To evaluate the effects of oxidative stress in the airway inflammation and remodeling of high-fat diet induced obese mice with asthma.Methods Sixty female C57/6J mice were randomly divided into four groups,ie.an asthma group,an obese group,an obese asthma group,and a control group.The mice in the asthma group were sensitized and challenged with ovalbumin（OVA） and fed with normal diets.The mice in the obese group were fed with high-fat diets.The mice in the obese asthma group were sensitized and challenged as the asthma group,and fed as the obese group.The mice in the control group were sensitized and challenged with normal saline and fed with normal diets.After 12 weeks,bronchoalveolar lavage fluid（BALF） were collected for total and differential cell count.IL-6 and 8-iso-prostaglandin F2α（8-iso-PGF2α） in lung tissue homognate were detected by ELISA.The pathological changes were observed under light microscope by HE staining.Meanwhile the remodeling indices including total bronchial wall area（WAt）,smooth muscle area（WAm）,and bronchial basement membrane perimeter（Pbm） were measured.Results In comparison with the obese group and the asthma group,the leukocytes and eosinophils in BALF,WAt/ Pbm,and IL6 in lung tissue increased significantly in the obese asthma group（P0.05）.8-iso-PGF2α in lung tissue increased in sequence of the control group,the obese group,the asthma group,and the obese asthma group significantly.Pearson correlation analysis showed that leukocyte in BALF,WAt/ Pbm,and IL-6 were in positive correlation with 8-iso-PGF2α（r=0.828,0.863,0.891,respectively,P0.01）.Conclusion Oxidative stress is involved in the airway inflammation and remodeling of obese asthma mice with high-fat diets.