Positive correlation between PPARγ,PGC-1αandγ-GCS in lungs of rats and patients with chronic obstructive pulmonary disease
会议名称：《中国生理学会第23届全国会员代表大会暨生理学学术大会》
会议日期：2010年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
关 键 词：peroxisome proliferator-activated receptor gamma peroxisome proliferator-activated receptorγcoactivator-1 γ-glutamylcysteine synthetase chronic obstructive pulmonary disease
摘 要：正Oxidative stress is one of the major pathogenesis of chronic obstructive pulmonary disease（COPD）.γ-Glutamylcysteine synthetase（γ-GCS） is one of the paramount antioxidant enzymes in *** proliferatoractivated receptor gamma（PPARγ） is a ligand-activated transcription factor,which is activated by specific ligands such as rosiglitazone（RGZ）,exerting multiple biological ***γcoactivator-1α（PGC-1α） is a PPARγcoactivator, which binds to PPARγby induction of PPARγligands,co-activating PPARγtarget *** evidence has suggested that PPARγ/PGC-1αcan regulate multiple antioxidant ***,the effect of PPARγ/ PGC-1αonγ-GCS during the development of COPD remains unclear *** measured the expression levels of PPARγ,PGC-1αandγ-GCS,γ-GCS activity and reactive oxygen species（ROS） contents in lungs of rats treated by cigarette smoke（CS）+lipopolysaccharide（LPS） and CS+LPS+RGZ,as well as lungs of patients suffering from *** with lungs from CS+LPS-treated rats,lungs of RGZ-treated rats demonstrated markedly lower ROS contents,and remarkable increase ofγ-GCS activity and increase of the expression levels of PPARγ,PGC-1αandγ-***,compared with controls,expression levels of PPARγ,PGC-1αandγ-GCS significantly increased in lungs of mild COPD patients,and progressively decreased in lungs of patients with moderate and severe COPD.γ-GCS protein was positively correlated with FEV1%.PPARγand PGC-1αproteins were positively correlated withγ-GCS activity and mRNA *** conclusion,γ-GCS showed compensatory up-regulation in the early stage of COPD,which progressively decompensate with increasing COPD *** activation of the PPARγ/PGC-1αpathway may protect against COPD progression by up-regulatingγ-GCS and relieving oxidative stress.