PPAR-γ激动剂对哮喘小鼠气道重塑的影响

Effect of PPAR-γ agonist on airway remodeling in asthmatic mice

目的探究过氧化物酶增值物激活受体-γ(PPAR-γ)激动剂吡格列酮对哮喘小鼠气道重塑的相关作用及对肺组织中脂联素表达的影响。方法将24只雌性C57小鼠随机分为正常对照组(Con组)、哮喘组(OVA组)、药物组(OVA+ROSI组),利用卵清蛋白(OVA)致敏和激发制作慢性哮喘模型,OVA+ROSI组每次激发前给予10 mg/(kg·d)吡格列酮灌胃,Con组及OVA组给予相同容积生理盐水灌胃,HE染色显微镜下检测气道上皮损伤情况,Masson染色显微镜下检测气道重塑程度,real-time PCR检测肺组织中脂联素受体1(AdipoR1)、AdipoR2、PPAR-γmRNA表达。蛋白质免疫印迹法检测肺组织中PPAR-γ、脂联素(ADPN)的表达水平。结果与Con组比较,OVA气道损伤程度及胶原沉积明显增多,肺组织中PPAR-γ升高,AdipoR1、AdipoR2、ADPN水平降低,差异均有统计学意义(P<0.01);与OVA组比较,OVA+ROSI组气道损伤程度及胶原沉积面积有所减少,仍较Con组增加;OVA+ROSI组肺组织中PPAR-γ、Adipo R1、AdipoR2 mRNA及蛋白水平均较Con组、VOA组增加,ADPN表达水平升高,差异均有统计学意义(P<0.01)。结论 PPAR-γ激动剂吡格列酮具有抑制慢性哮喘小鼠气道炎症与气道重塑的作用,其中机制可能与通过PPAR-γ途径上调ADPN的表达相关。

Objective To investigate the effect of PPAR-γ agonist pioglitazone on airway remodeling in asthmatic mice and its effect on adiponectin expression in lung tissue. Methods The 24 female C57 mice were randomly divided into normal control group(Con group),asthma group(OVA group)and drug group(OVA + ROSI group). The model of chronic asthma was induced by sensitization and activation of ovalbumin(OVA). The OVA+ROSI group was given 10 mg(kg · d)pioglitazone irrigation before each excitation,the Con group and the OVA group were given the same volume of normal saline,the HE staining microscope to detect airway epithelial injury,Masson staining microscope to detect airway remodeling,the expression of PPAR-γ mRNA and adiponectin receptor 1(AdipyR1),AdipoR2 mRNA in lung tissue were detected by real-time PCR.Western blotting was used to detect the expression of PPAR-γ and Adiponectin(ADPN)in lung tissue. Results Compared with the Con group,the degree of airway injury and collagen deposition in the OVA group were significantly increased,the expression of PPAR-γ in the lung tissue,the expression of Adipy R1,AdipoR2 and ADPN decreased,the differences were statistically significant(P<0.01).Compared with the OVA group,the degree of airway injury and the area of collagen deposition were decreased in the OVA+ROSI group,which was still higher than that in the Con group;the expression of PPAR-γ,AdipyR1,AdipoR2 mRNA and adiponectin in lung tissue increased,the differences were statistically significant(P<0.01). Conclusion PPAR-γ agonist pioglitazone has the effect of inhibiting airway inflammation and airway remodeling in chronic asthmatic mice,and the mechanism may be related to the up-regulation of ADPN expression by PPAR-γ pathway.