罗格列酮对慢性阻塞性肺疾病患者过氧化物酶体增殖物激活受体-γ信号通路的影响  

Effects of rosiglitazone on peroxisome proliferator activated receptor-γ pathway in patients with chronic obstructive pulmonary disease

作　　者：曾晓丽[1] 刘晓菊[1] 包海荣[1] 张艺[1] 谭恩丽[1] 廖剑敏[1] 

机构地区：[1]兰州大学第一医院老年呼吸科,730000

出　　处：《中华结核和呼吸杂志》2011年第10期743-748,共6页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家自然科学基金（81070038）;中央高校基本科研业务费专项资金（lzujbky-2011-103）

摘　　要：目的探讨罗格列酮对COPD患者过氧化物酶体增殖物激活受体-γ（PPAR-γ）、核因子-κB及肿瘤坏死因子-α（TNF-α）的影响。方法2010年4—11月，选择COPD急性加重期患者30例，其中男22例，女8例，年龄54～87岁，平均（72±9）岁；健康体检者（对照组）24例，其中男18例，女6例，年龄52～80岁，平均（69±10）岁。抽取受试者空腹肘静脉血10ml，分离培养外周血单个核细胞（PBMCs）。将30例COPD患者的PBMCs均分为3份，分别根据不同的药物干预分为非干预组、罗格列酮干预组（罗格列酮组）和罗格列酮联合GW9662干预组（联合干预组），对照组PBMCs不加任何药物干预。采用实时荧光定量PCR检测PBMCs中PPAR-γ和核因子-κB的mRNA表达，细胞免疫荧光法结合激光扫描共聚焦显微镜检测PPAR-γ和核因子-κB蛋白表达及核转位，酶联免疫吸附试验检测细胞培养上清液中TNF-α含量。多组间比较采用方差分析，组间两两比较采用LSD—t检验，相关性分析采用Pearson检验。结果mRNA（2^-△△Ct值）和蛋白表达（荧光强度值）：非干预组PPAR-γ（0．52±0．10和55±11）低于对照组（1和85±9），核因子-κB（1．69±0．07和145±17）高于对照组（1和118±7）；罗格列酮组PPAR-γ（4．47±0．11和204±12）高于非干预组，核因子-κB（0．33±0．04和59±14）低于非干预组；联合干预组PPAR-γ（2．25±0．31和142±23）低于罗格列酮组，高于非干预组，核因子-κB（0．64±0．02和90±10）高于罗格列酮组，低于非干预组；组间比较差异均有统计学意义（F值为29．21～567．42，均P〈0．01）。TNF-α浓度（μg/L）：非干预组（96．2±1．4）高于对照组（85．3±1．0），罗格列酮组（63．0±2．5）低于非干预组，联合干预组（83．3±1．9）高于罗格列酮组，低于非干预组，组间比较差异有统计学意义（F值为293．72，P〈0．01）。非干预�Objective To explore the effects of rosiglitazone on peroxisome proliferator activated receptor-α （PPAR-γ）, nuclear factor-κB and tumor necrosis factor-α （TNF-α） in patients with chronic obstructive pulmonary disease （COPD）. Methods From Apr. 2010 to Nov. 2010, 30 patients with acute exacerbations of COPD, 22 males and 8 females, age 54 - 87 （ mean 72 ± 9） years and 24 healthy controls, 18 males and 6 females, age 52 - 80 （mean 69 ± 10 ） years were included. The peripheral blood mononuclear cells （PBMCs） were isolated from venous blood and then cultured. On the basis of the treatment given, the PBMCs of COPD patients were divided into 3 groups ： non-treatment group, rosiglitazone treatment group （rosiglitazone group） and rosiglitazone and GW9662 treatment group （combined treatment group）. Cells from the healthy controls （control group） did not receive any drug treatment. The mRNA expression of PPAR-γand NF-κB was measured with real-time PCR. The protein expression and nuclear translocation of PPAR-γand NF-κB were detected using immunofluorescence with laser scanning confocal microscopy. The TNF-α level in culture supernatant was measured with ELISA. One-way ANOVA and LSD- t test and the Pearson correlation coefficient were used for statistical analysis. Results The mRNA and protein levels of PPAR-γwere lower in the non-treatment group （0. 52 ±0. 10, 55 ± 11 ） than those in the control group （1, 85 ±9）, while the levels of NF-κB mRNA and protein were higher in the non-treatment group （ 1.69 ±0. 07, 145 ± 17） than those in the control group （ 1, 118 ±7）. The mRNA and protein levels of PPAR-γin the rosiglitazone group （4. 47 ± 0. 11, 204 ± 12） were significantly increased compared with the non-treatment group, while the mRNA and protein levels of NF-κB （ 0. 33 ± 0. 04, 59 ± 14 ） were remarkably decreased compared with the non-treatment group. The mRNA and protein levels of PPAR-γ（2. 25 ±0. 31, 142 ± 23） were significantly

关 键 词：肺疾病 慢性阻塞性 过氧化物酶体增殖物激活受体 罗格列酮 NF—κB 肿瘤坏死因子Α 

分 类 号：R96[医药卫生—药理学]