过氧化物酶体增殖物活化受体γ在哮喘气道血管重构中的作用

Effect of PPARγ on the airway vascular remodeling in the asthmatic mice

目的探讨过氧化物酶体增殖物活化受体γ(PPARγ)在哮喘小鼠气道血管重构中的作用。方法 50只小鼠随机分为5组:对照组、激动组、拮抗组、激素组和哮喘组。卵白蛋白雾化吸入建立小鼠哮喘模型,观察支气管肺泡灌洗液、肺组织中炎症反应和重构情况;并以western blot技术测定肺组织中PPARγ的表达水平,比较其与重构程度的关系。结果哮喘组血管管壁厚度[(4.66±0.73)μm]和血管旁胶原纤维沉积量[(22.1±2.42)μm^2/μm]较对照组[(2.87±0.46)μm、(1.73±0.73)μm^2/μm]明显增加;激动组和激素组中这一变化均较哮喘组明显减轻,且两组间比较无显著性差异。血管管壁厚度与气道平滑肌厚度或气道旁胶原纤维面积(r=0.576、0.692,P<0.01)以及血管旁胶原纤维面积与气道平滑肌厚度或气道旁胶原纤维面积呈正相关(r=0.825、0.928,P<0.01)。除激素组外,核内PPARγ的表达水平与气道平滑肌厚度、气道旁胶原纤维面积和血管旁胶原纤维面积呈负相关(r=-0.73、-0.85、-0.91,P<0.01),而与血管管壁厚度无相关性。结论 PPARγ激动剂通过促进PPARγ的核定位,抑制哮喘的气道炎症和气道重构。

Objective To explore the effect of PPARγ on the airway vascular remodeling in the asthmatic mice. Methods A mouse model of asthma induced by sensitization and airway challenged with ovalbumin. Rosiglitazone （a PPARγ agonist）, GW9662 （a PPARγ antagonist） and budesonide were administered by means of nebulization in rosiglitazone group （RG）,GW9662 group （GG） and budesonide group （BG） respectively. The thickness of airway vascular wall and collagen deposition around airway vessels were measured and recorded, along with the parameters associated with airway inflammation （the cells count and the IL-4 level in the bronchoalveolar lavage fluid,and the inflammation cell score around the airway） and airway remodeling （the goblet cell hyperplasia in the lumens,thickness of airway smooth muscle and amount of collagen deposition around the bronchus）. The expression of PPARγ was assaged by western blot. Results Above all assessed parameters were higher in AG than in CG, special for the thickness of airway vascular wall [（4.66±0.73） μm vs （2.87±0.46） μm]and collagen deposition around airway vessels [（22.1±2.42） μm^2/μm vs （1.73 ± 0.73） μm^2/μm], and were reduced by treatment of rosiglitazone [（ 3.95 ± 0.90） and （9.97±1.56） μm^2/μm] or budesonide [（4.67±0.71） and （22.5±2.58） μm^2/μm] significantly （P〈0.01）. No difference was observed in the improvement of airway remodeling and vascular remodeling between RG and BG. There were a significant negative correlation between nuclear PPARγ and collagen deposition around vessel （ r =-0.91, P〈0.01）, but not the thickness of vascular wall in the 4 groups except for BG. Conclusions Rosiglitazone, a PPARγ agonist, inhibited the airway vascular remodeling as budesonide in asthmatic mice.