慢性阻塞性肺疾病患者转录因子、糖皮质激素受体的表达

The expression of transcription factors and glucocorticoid receptors of chronic obstructive pulmonary disease

目的:探讨慢性阻塞性肺疾病(COPD)患者转录因子活化蛋白-1(AP-1)、核因子-κB(NF-κB)、糖皮质激素受体(GR)的表达水平及不同治疗后的变化。方法:36例COPD急性发作期患者随机分为激素治疗组(18例)与非激素治疗组(18例),18例健康者为对照组;激素治疗组给予续贯的糖皮质激素治疗及常规治疗,非激素治疗组给予除激素之外的常规治疗,用荧光定量RT-PCR方法测定外周血单核细胞c-jun(代表AP-1)、核转录因子κB(NF-κB)、糖皮质激素受体(GR-α和GR-β)mRNA的表达水平。结果:COPD患者c-jun、NF-κB表达水平始终高于健康对照组;治疗后与治疗前相比,激素治疗组c-jun和NF-κB显著下降,非激素治疗组NF-κB有显著下降,c-jun有下降趋势,但差异无统计学意义。治疗前COPD患者GR-α表达水平显著低于健康对照组,GR-β表达水平显著高于健康对照组;治疗后COPD患者GR-α表达水平较治疗前升高,GR-β表达水平较治疗前下降。激素治疗组治疗前C-jun、NF-κB、GR-α、GR-β分别为0.093±0.047、0.122±0.062、0.062±0.035、0.102±0.026;非激素治疗组分别为0.094±0.053、0.123±0.045、0.065±0.034、0.095±0.031;两组比较,差异无统计学意义,P>0.05;激素治疗组治疗3个月时C-jun为0.054±0.024,非激素治疗组治疗3个月时C-jun为0.076±0.015,两组比较差异有统计学意义,P<0.05。结论:COPD患者c-jun、NF-κB、GR-α和GR-β的表达量与健康者存在差异,这可能是COPD炎症反应的基础,这些可能成为治疗COPD炎症反应的新靶向。

Objective：To study the expression of transcription factors including activator protein-1（AP-1）,nuclear factor-κB（NF-κB） and glucocorticoid receptors（GR） of chronic obstructive pulmonary disease（COPD） and the changes after different treatment.Methods：36 cases COPD patients with acute exacerbation were randomly divided into glucocorticoid treatment group and non-glucocorticoid treatment group 18 cases of healthy people as control group.The glucocorticoid treatment group was given sequential glucocorticoid and regular treatment.The non-glucocorticoid treatment group was given regular treatment except glucocorticoid.The mRNA levels of c-jun（insteading of AP-1）,NF-κB,GR αand GRβ were evaluated by reverse transcription-polymerase chain reaction（RT-PCR） before and after treatment.Results：Before and after treatment,the levels of c-jun and NF-κB were significantly higher than healthy subjects.After treatment,the levels of c-jun and NF-κB in glucocorticoid treatment group were significantly decreased than before treatment.In non-glucocorticoid treatment group,the level of NF-κB was significantly decreased and the level of c-jun was indistinctively decreased compared with before treatment.Before treatment,in COPD patients the level of GR αwas lower and the level of GRβ was higher than healthy subjects.After treatment,the level of GR-α was higher and the level of GR-β was lower than before.Before hormone treatment,C-jun,NF-κB,GR-α,GR-β were 0.093 ±0.047,0.122± 0.062,0.062±0.035,0.102±0.026;non-hormonal treatment group were 0.094 ± 0.053,0.123±0.045,0.065±0.034,0.095±0.031;there was no significant difference,P0.05;in hormone treatment group,C-jun was 0.054±0.024 after 3 months treatment,and it was 0.076±0.015 in non-hormonal treatment group,difference between the two groups was significant,P0.05.Conclusion：The expression levels of AP-1,NF-κB,GR-α and GR-β of COPD patients were different from healthy people.These factors may be the bases of inflammatory of COPD and may also be a new target for novel anti-inflammatory treatment.