PPAR-γ/PGC-1α对支气管哮喘豚鼠肺组织Nrf2/γ-GCS-h作用  

The Roles of PPAR-γ/PGC-1α to Nrf2/γ-GCS-h in lung of guinea pigs with bronchial asthma

作　　者：陈健[1] 戴爱国 傅满姣[1] 龙章改[1] 朱黎明 

机构地区：[1]湖南省长沙市中心医院胸科中心七病室,长沙410004 [2]湖南省老年医院-湖南省老年医学研究所呼吸疾病研究室,长沙410016

出　　处：《中国应用生理学杂志》2011年第2期225-229,260,共6页Chinese Journal of Applied Physiology

基　　金：湖南省医药卫生科研计划课题项目(B2007169);湖南省科技计划项目(05JT1024)

摘　　要：目的:观察PPAR-γ、PGC-1α、Nrf2和γ-GCS-h在豚鼠支气管哮喘肺组织中表达而探索PPAR-γ/PGC-1α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(C组)和罗格列酮治疗组(D组),每组10只豚鼠,卵蛋白致敏法复制哮喘模型。原位杂交检测PPAR-γ、PGC-1α、Nrf2和γ-GCS-hmRNA表达,免疫组化和Western blot检测四种蛋白表达。结果:PPAR-γ、PGC-1α、Nrf2和γ-GCS-h的mRNA哮喘组表达最低,四组表达差异有统计学意义(P均<0.01);免疫组化和Western blot显示PPAR-γ、PGC-1α、Nrf2和γ-GCS-h的蛋白哮喘组表达几乎都呈阴性而且以核内表达为主,四组差异均有统计学意义(P均<0.01)。PPAR-γ表达与PGC-1α表达呈正相关,γ-GCS-h mRNA表达与PPAR-γ、PGC-1α、Nrf2核内表达均呈正相关,Nrf2表达与PPAR-γ和PGC-1α表达均呈正相关。结论:PPAR-γ、PGC-1α、Nrf2和γ-GCS-h在卵蛋白致敏急性支气管哮喘模型中表达下降;PPAR-γ/PGC-1α可通过上调Nrf2/γ-GCS-h表达提高组织的抗氧化能力,因而PPAR-γ/PGC-1α在哮喘的发病和防治可能起重要的作用。Objective：To investigate the expressions of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h in lung of guinea pigs with bronchial asthma,and to explore the roles of them.Methods：Forty adult male guinea pigs were randomly divided into 4 groups：the control group（group A）,asthmatic group（group B）,dexamethasone group（group C） and rogridone group（group D）,10 guinea pigs in each group.The asthmatic model was established by the ovalbumin challenge method.Expressions of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h mRNA in lung tissue were assayed by in situ hybridization.Expressions of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h protein were detected by immunohischemistry and by Western blot.Results：In situ hybridization showed that the expressions of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h mRNA in lung tissue were the lowest in group B and the comparison among groups showed statistical significant（all P0.01）.Immunohistochemistry and Western blot indicated that the value of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h protein in lung tissue were the lowest in group B,and expressed primarily in nucleus,the differences being statistically significant（all P0.01）.There was positive correlation between PPAR-γ and PGC-1.γ-GCS-h mRNA also positively correlated between PPAR-γ/PGC-1α and Nrf2 in nucleus,and the expression of Nrf2 was also positively correlated with PPAR-γ/PGC-1α.Conclusion：In acute asthmatic models induced by ovalbumin,the expressions of PPAR-γ/PGC-1α and Nrf2/γ-GCS-h were decreased,and PPARγ/PGC-1α could up-regulate the expressions of Nrf2/γ-GCS-h to increase the antioxidant defense of tissues,thus being implicated that PPARγ/PGC-1α might play important roles in the pathogenesis and prevention of asthma.

关 键 词：支气管哮喘 过氧化物酶体增殖物激活受体-Γ 过氧化物酶体增殖物激活受体协同刺激因子-1α 谷氨酰半胱氨酸合酶重链 红系衍生的核因子2相关因子2 

分 类 号：R73-3[医药卫生—肿瘤]