基础医学与临床 ›› 2016, Vol. 36 ›› Issue (3): 380-385.

• 研究论文 • 上一篇    下一篇

Adipo/AMPK信号通路的下调参与肥胖型哮喘小鼠的发病

陈秀珍1,崇蕾1,林罗娜1,孔璐丹1,李昌崇2   

  1. 1. 温州医科大学附属第二医院
    2. 温州医学院育英儿童医院呼吸内科
  • 收稿日期:2015-09-07 修回日期:2015-12-06 出版日期:2016-03-05 发布日期:2016-02-22
  • 通讯作者: 李昌崇 E-mail:wzlichch@21cn.com

Down—regulation of Adipo/AMPK signaling is involved in the pathogenesis of obesity-related asthma

  • Received:2015-09-07 Revised:2015-12-06 Online:2016-03-05 Published:2016-02-22

摘要: 目的 探讨Adipo/AMPK信号通路在肥胖型哮喘气道炎性反应及气道高反应中的作用及机制。方法 将40只SPF级C57BL/6小鼠随机分为正常体质量组(A)、哮喘组(B)、肥胖组(C)和肥胖哮喘组(D),A组进行普通饲料喂养+0.9%NaCL致敏激发,B组进行普通饲料喂养+OVA/Al(OH)3致敏激发,C组予以高脂饲料喂养+0.9% NaCL致敏激发,D组则给予高脂饲料喂养+OVA/Al(OH)3致敏激发。测定各组小鼠气道阻力,HE染色观察肺组织病理改变,ELISA法检测血清Adipo水平,qRT-PCR法检测肺组织Adipo、AdipoR1及AMPKα mRNA的表达,Western blot法检测肺组织Adipo、AMPKα和pAMPKα蛋白的表达水平。结果 C组和D组小鼠体质量增长明显(P<0.01);与A组相比,B组、C组和D组总气道阻力(RL)增高、肺部炎性反应加重,D组增高最显著(P<0.05);同时,B组、C组和D组小鼠肺组织Adipo mRNA、AdipoR1 mRNA、Adipo蛋白和pAMPKα蛋白的表达较A组显著降低(P<0.05)。结论 肥胖型哮喘小鼠气道反应增高、气道炎性反应加重可能与Adipo/AMPK信号通路的下调有关。

关键词: 哮喘, 肥胖, 脂联素, AMPK

Abstract: Objective To investigate the potential effect of adiponectin/ AMP-activated protein (AMPK ) signaling pathway on the airway inflammation and airway hyperreactivity in obesity-related asthma. Methods Forty male C57BL/6 mice were randomly divided into four groups, which were designed as control group(A), asthma group(B) ,obese group(C) and obese asthma group(D). The mice in group A were fed with normal diet , sensitized and challenged with saline. The mice in group B were sensitized and challenged with ovalbumin(OVA) and fed with normal diet. The mice in group C and D were fed with high fat diet, the mice in group D were sensitized and challenged with OVA and the mice in group C used saline instead. After 12 weeks, airway resistances(RL) were determined and the histopathologies of lung tissues were observed .Real-time PCR was used to detect the expressions of adiponectin mRNA、AdipoR1 mRNA and AMPKα mRNA and Westem blotting was used to detect the expressions of adiponectin、phosphor-AMPKα(pAMPKα) and AMPKα proteins.Results The mean weight of high fat food feeding mice was 20% higher than mice feeding with normal diet and achieved the standard of obesity at the 12 weeks after feeding, the difference was significant(P<0.01). Compared to group A, the expression level of adiponectin mRNA,AdipoR1 mRNA as well as the adiponectin protein and pAMPKα protein in lung were significantly decreased in the other three groups with group D most obviously(P<0.05).Conclusions The airway responsiveness was higher in obesity-related asthma, which may partly due to the down-regulation of Adipo/AMPK signaling pathway.

Key words: asthma, obesity, adiponectin, AMPK

中图分类号: