过氧化物酶体增殖物激活受体γ在哮喘气道炎症中的作用

The effect of PPAR_γ on the airway inflammation in the asthmatic mice

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)在哮喘小鼠气道炎症中的作用。方法5O只小鼠随机分为5组:激动组、激素激动组、激素组、哮喘组和对照组。卵白蛋白雾化吸入建立小鼠哮喘模型,计数支气管肺泡灌洗液(BALF)中嗜酸粒细胞数,观察支气管肺组织病理的改变,ELISA测定血清中IL-4的水平,采用RT-PCR方法检测肺组织中PPARγmRNA的表达,肺组织病理切片做PPARγ免疫组化染色、计数PPARγ阳性细胞数。结果哮喘组小鼠支气管肺泡灌洗液中嗜酸粒细胞数明显高于其它各组,应用罗格列酮的激动组和激素激动组低于哮喘组,但激动组仍高于激素组。肺内炎症细胞评分显示哮喘组评分最高,对照组评分最低,激素组评分低于激动组。各组血清中IL-4的水平(pg/ml)分别为152.24±1.54、127.88±2.31、128.13±2.05、164.39±4.90、124.07±3.66。哮喘组IL-4的含量显著高于其余各组,与激动组比较,P<0.05;与另外3组比较,P<0.001。各组肺组织的PPARγmRNA水平分别为26.70±0.52、25.00±0.75、17.70±0.42、19.30±0.50、15.00±0.49,OVA吸入后PPARγ表达增加,应用PPARγ激动剂后PPARγ表达进一步增加,差异有统计学意义。各组肺组织PPARγ阳性细胞数分别为18.40±0.67、16.10±0.97、10.20±0.42、13.10±0.82、7.50±0.72,应用PPARγ激动剂后阳性细胞数高于哮喘组、激素组、对照组,有显著性差异。结论PPARγ在哮喘的气道炎症过程中具有抗炎症作用,PPARγ激动剂能减轻哮喘气道炎症。

Objective To explore the effect of PPARγ on the airway inflammation in the asthmatic mice. Methods A mouse moel of asthma induced by sensitization and airway challenged with ovalbumin.50 female BALB/c mice were divided into 5 groups： matched Rosiglitazone treatment group （A）, Resiglitazone ＋ BUD treatment group （B）, BUD treatment group （C）, asthma group （D）, and control group （E）. We counted the EOS in the BALF and observed the lung tissue with microscope. We detected the serum level of IL-4 by ELISA and detected PPARγ mRNA in the lung by RT-PCR. Pathological section of lung was stained by immunohistochemistry, then We calculated positive cells. Results EOS of Group D was significantly higher than others. Group A and B was lower than D, however,A was still higher than C. Score of inflammatory cell in lung showed that D was the highest, E wais lowest,C was lower than A.Levels of IL-4 （pg/ml）in serum d the five groups were 152.24 ± 1.54,127.88 ± 2.31,128.13±2.05,164.39±4.90, 124.07 ± 3.66. IL-4 level of group D was higher than that of the others. The levels of PPARγ mRNA of the five groups were 26.70 ±0.52,25.00±0.75,17.70±0.42,19.30±0.50,15.00±0.49, After OVA inhalation, the PPARγ expressing increased and even further after Rosiglitazone administrated. The differences were significant. The numbers of PPARγ positive cells in immunohistochemistry of each group were 18.40±0.67,16.10±0.97,10.20±0.42,13.10±0.82,7.50±0.72,PPARγ positive cells of group D were more than E.Group A and B were more than D,C and E.Group C was less than D. Conclusion PPARγ has some anti-inflammatory role in asthma airway irtflammafion. Rosiglitazone, a PPARγagonist can reduce the airway inflammation in asthma mice.