支气管哮喘豚鼠BALF炎症细胞中PPARγ、Nrf2和γ-GCS-h表达的变化  

Expression of PPARγ,Nrf2 and γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid of guinea pigs with bronchial asthma

作　　者：陈健[1,2] 戴爱国 胡瑞成 朱黎明 

机构地区：[1]湖南省老年医院-湖南省老年医学研究所呼吸疾病研究室,湖南长沙410016 [2]南华大学研究生院,湖南衡阳421001

出　　处：《中国病理生理杂志》2010年第4期760-765,共6页Chinese Journal of Pathophysiology

基　　金：湖南省医药卫生科研计划资助项目(No.B2007169);湖南省科技计划资助项目(No.05JT1024)

摘　　要：目的:研究支气管哮喘急性发作豚鼠肺泡灌洗液(BALF)炎症细胞中PPARγ、Nrf2和γ-GCS-h表达变化并探索PPARγ对Nrf2/γ-GCS-h作用。方法:40只健康雄性豚鼠随机化原则分成对照组(A组)、哮喘组(B组)、地塞米松组(C组)和罗格列酮组(D组),每组10只豚鼠,卵蛋白致敏法复制哮喘模型。收集BALF,行细胞计数和分类,离心,上清液行活性氧(ROS)和丙二醛(MDA)浓度测定,细胞涂片原位杂交检测PPARγ、Nrf2和γ-GCS-hmRNA表达,细胞涂片免疫细胞化学检测PPARγ、Nrf2和γ-GCS-h蛋白表达。结果:B组嗜酸性粒细胞数(EOS)比例高于A组、C组和D组,差异显著(P<0.01),BALF中ROS和MDA浓度在B组中最高,4组间差异显著(均P<0.05);PPARγ、Nrf2和γ-GCS-hmRNA和蛋白在B组表达最低,4组表达差异显著(均P<0.01)。PPARγ与Nrf2/γ-GCS-h表达均呈正相关(均P<0.05);γ-GCS-h与Nrf2表达呈正相关(r=0.954,P<0.05);哮喘组PPARγ、γ-GCS-h和Nrf2表达均与浸润的嗜酸性粒细胞数呈负相关(均P<0.05)。结论:PPARγ和Nrf2/γ-GCS-h在卵蛋白致敏急性支气管哮喘模型BALF炎症细胞中表达均下降;PPARγ可上调Nrf2/γ-GCS-h表达,在抑制炎症反应和氧化应激中发挥重要作用,这可能为支气管哮喘防治开辟新途径。AIM：To investigate the expression of PPARγ and Nrf2/γ-GCS-h in inflammatory cells in bronchoalveolar lavage fluid（BALF） of guinea pig with bronchial asthma of acute episode,and to explore the roles of PPARγ on Nrf2/γ-GCS-h expression. METHODS： Forty adult male guinea pigs were randomly divided into 4 groups （10 guinea pigs in each group）： control group （group A）,asthmatic group （group B）,dexamethasone treatment group （group C） and rogridone treatment group （group D）. The asthmatic model was established by an ovalbumin challenge method. BALF was collected,and the total cell count and the proportion of the inflammatory cells were measured. After centrifugation,the concentrations of ROS and MDA in the clear supernatant were detected. The methods of in situ hybridization and immunohistochemistry were used for detecting the expression of PPARγ and Nrf2/γ-GCS-h at mRNA and protein levels. RESULTS： The proportion of eosinophils （EOS） in BALF in group B was significantly higher than that in groups A,C and D （P〈0.01）. The concentrations of ROS and MDA in BALF of group B was the highest. The difference of ROS and MDA was statistically significant （all P〈0.05） as compared to the control. The results of immunohistochemistry and in situ hybridization indicated that the A value was the lowest in group B as compared to that in groups A,C and D （all P〈0.01）. In group B,the positive correlations were observed between PPARγ and Nrf2/γ-GCS-h,between γ-GCS-h and Nrf2. A negative correlation between the proportion of EOS in BALF and the expression of PPARγ and Nrf2/γ-GCS-h was also observed （all P〈0.05）. CONCLUSION： In acute asthmatic models induced by ovalbumin,the expression of PPARγ and Nrf2/γ-GCS-h is decreased,and PPARγ may up-regulate the expression of Nrf2/γ-GCS-h to inhibit the inflammatory and oxidative reactions,indicating a new way for prevention and treatment of bronchial asthma.

关 键 词：哮喘 过氧化物酶体增殖物激活受体-Γ 谷氨酰半胱氨酸合酶重链 核因子E2相关因子-2 

分 类 号：R562.25[医药卫生—呼吸系统]