过氧化物酶体增殖活化受体γ对支气管哮喘豚鼠气道炎症的影响

Influence of peroxisome proliferator-activated receptor gamma on airway inflammation of guinea pigs with asthma

目的 探讨过氧化物酶体增殖活化受体γ (PPAR γ)和PPAR γ配体激动剂罗格列酮对支气管哮喘 (简称哮喘 )豚鼠气道炎症的影响及机制。方法 35只豚鼠按随机数字表法分为对照组(A组 )、哮喘组 (B组 )、地塞米松 (DXM)组 (C组 )、罗格列酮组 (D组 )、罗格列酮 +1/ 2DXM用量组 (E组 ) ,每组各 7只。并测定各组豚鼠支气管肺泡灌洗液 (BALF)中细胞计数及分类 ,观察各组豚鼠支气管肺组织病理的改变 ;采用逆转录 聚合酶链反应 (RT PCR)方法检测豚鼠肺组织中PPAR γ、还氧化酶2 (COX 2 )等的表达。结果 D组豚鼠BALF中的嗜酸粒细胞数为 0 0 5 0± 0 0 2 0 ,B组为 0 110± 0 0 2 0 ,两组比较差异有显著性 (t=5 6 1,P <0 0 0 1) ,D组豚鼠BALF中的细胞总数、中性粒细胞数分别为(15 5± 3 9)× 10 8/L、0 0 6 9± 0 0 2 0 ,B组分别为 (19 9± 4 3)× 10 8/L、0 0 76± 0 0 2 0 ,两组比较差异无显著性 (t值分别 =2 0 2、0 6 6 ,P均 >0 0 5 ) ;D组豚鼠气道壁厚度为 (2 2 0± 5 0 ) μm ,B组为 (2 8 0± 5 0 )μm ,两组比较差异有显著性 (t=2 6 1,P <0 0 5 ) ,但D组黏膜及黏膜下层厚度 [(12 2± 2 9) μm]与B组[(14 9± 3 3) μm]比较差异无显著性 (t =1 6 3,P >0 0 5 ) ;D组PPAR

Objective To investigate the influence and mechanism of peroxisome proliferator activated receptor gamma(PPAR γ) and its ligand agonist rosiglitazone on airway inflammation of guinea pigs with asthma Methods 35 guinea pigs were divided into 5 groups by random number meter: a control group(A group), an asthma group(B group), a dexamethasone(DXM) group(C group), a rosiglitazone group(D group), and a rosiglitazone + 1/2 DXM group (E group), with 7 guinea pigs in each Bronchoalveolar lavage (BAL) cell count and differential was studied, and the pathologic alteration of the bronchi and the lung tissue was observed The expression of PPAR γ、 COX 2 was measured by RT PCR Results BAL eosinophil count was 0 050±0 020 in D group, 0 110±0 020 in B group, the difference being significantly ( t =5 61, P <0 001) The total cell number and neutrophils were (15 5±3 9)×10 8/L and 0 069±0 020 in D group, and (19 9±4 3)×10 8/L and 0 076±0 020 in B group, the difference being not significant( t =2 02,0 66, P >0 05 respectively) The thickness of airway wall of D group was (22 0±5 0)μm , and in B group it was (28 0± 5 0)μm, the difference being significant( t =2 61, P <0 05), but the thickness of mucosa and submucosa of D group (12 2±2 9)μm was not different as compared with B group (14 9±3 3)μm ( t =1 63, P >0 05) Expression of PPAR γ mRNA of D group 19 5±3 0 was not different compared with B group 18 1±3 1 and A group 15 6±2 9 respectively( t =0 92, 0 49, P >0 05, respectively) When the expression of COX 2 mRNA of B group 49±7 was compared with D group 39±6, the difference was significant ( t =2 77, P <0 05) Conclusions Rosiglitazone decreases airway eosinophils and the thickness of airway wall in guinea pigs with asthma, via suppression of COX 2 mRNA expression by activating PPAR γ The anti inflammatory effect of PPAR γ may be associated with the use of ligand agonist and (or) glucocorticoids