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目的探讨转化生长因子-β(TGF-β)对肥胖哮喘小鼠气道重塑的影响及吡非尼酮干预的作用。方法 75只C57BL/6J小鼠随机分为对照组(A组)、肥胖组(B组)、肥胖哮喘组(C组)、布地奈德治疗组(D组)、吡非尼酮治疗组(E组)5组,每组15只。肥胖小鼠以高脂饮食诱导肥胖模型,C、D、E组采用卵清蛋白致敏激发建立哮喘模型,对照组以普通饲料饲养,生理盐水致敏激发。D组以布地奈德悬液(0.5 mg/ml)雾化,E组以吡非尼酮(300 mg/kg)饮水干预,余组正常饮水。4周后收集支气管肺泡灌洗液(BALF)进行细胞计数及分类。肺组织切片观察小鼠气道炎症及重塑情况,测定气管壁总面积(WAt)、气管平滑肌面积(WAm)和管腔基底膜周长(Pbm)。采用酶联免疫吸附实验、蛋白质印迹法检测TGF-β水平。结果 C组小鼠BALF中白细胞总数、嗜酸性粒细胞百分比、TGF-β水平、气管壁厚度(WAt/Pbm)和平滑肌厚度(WAm/Pbm)均高于其他四组;E组BALF中嗜酸性粒细胞百分比、WAt/Pbm较D组减少(P均<0.05);TGF-β水平按照C、D、E、B、A组依次递减(P均<0.05),且与BALF中嗜酸性粒细胞百分比呈正相关(r=0.79,P均<0.01)。结论 TGF-β在肥胖哮喘小鼠气道中高表达,与气道重塑有密切关系。吡非尼酮能有效抑制TGF-β的表达,从而改善肥胖哮喘气道重塑。
Objective To investigate the effect of transforming growth factor-β (TGF-β) on airway remodeling in obese asthmatic mice and the intervention of pirfenidone. Methods 75 C57BL / 6J mice were randomly divided into control group (group A), obesity group (group B), obese asthma group (group C), budesonide treatment group (group D) and pirfenidone treatment group E group) 5 groups, 15 in each group. Obese mice were induced with high-fat diet to induce obesity. C, D, E groups were established asthma model by ovalbumin sensitization challenge. The control group was fed with normal diet and challenged with saline. Group D was buffered with budesonide suspension (0.5 mg / ml), group E was treated with pirfenidone (300 mg / kg), and the other group received normal drinking water. After 4 weeks, bronchoalveolar lavage fluid (BALF) was collected for cell counting and classification. Lung tissue sections were used to observe airway inflammation and remodeling. The total tracheal wall area (WAt), tracheal smooth muscle area (WAm) and luminal basement membrane perimeter (Pbm) were measured. Enzyme-linked immunosorbent assay was used to detect the level of TGF-β by Western blot. Results The total number of leucocytes, percentage of eosinophils, TGF-β, WAt / Pbm and WAm / Pbm in BALF in group C were higher than those in other four groups. The eosinophilic The percentages of granulocytes and WAt / Pbm in group B were lower than those in group D (all P <0.05). The level of TGF-β decreased in order of C, D, E, B and A The percentage was positively correlated (r = 0.79, P <0.01). Conclusion TGF-β is overexpressed in airway of obese asthmatic mice, which is closely related to airway remodeling. Pirfenidone can effectively inhibit the expression of TGF-β, thereby improving airway remodeling in obese asthma.