慢性阻塞性肺疾病激素不敏感与糖皮质激素受体核内转移的相关性

发布时间：2018-07-28 12:21

【摘要】：目的研究慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)对糖皮质激素不敏感是否与糖皮质激素受体(glucocorticoids receptor,GRα)的核内转移有关。方法将来自12例健康人、15例轻中度哮喘患者和15例COPD患者的人外周血单个核细胞(peripheral blood molecule cells,PBMC)进行体外培养。ELISA方法检测其IL-8蛋白质水平,并计算地塞米松(Dex)半抑制浓度。PBMC在Dex中培养0.5~6 h,通过Western blot检测GRα蛋白质水平,GRα的核内转移则通过免疫荧光和共聚焦显微镜来观测和分析评估。结果COPD患者PBMC较轻中度哮喘患者和健康志愿者对Dex相对不敏感。Dex半抑制率(IC50Dex)与糖皮质激素受体GRα核内转移呈负相关(r=-0.54,P=0.000 8)。Dex可诱导增加各组PBMC中的总GRα,但GRα胞内分布各组间存在差异。Dex可明显增加健康人及哮喘患者核内的GRα,但并未增加COPD患者核内GRα。健康人及哮喘患者的PBMC中,Dex预处理能显著抑制TNF-α诱导的IL-8分泌,而在COPD患者的PBMC中这种抑制作用不明显。结论 COPD对糖皮质激素的不敏感与GRα核内转移有关。GRα核内转移受抑制可能是造成糖皮质激素在COPD患者中发挥抑制炎性作用欠佳的原因之一。
[Abstract]:Objective to investigate whether the insensitivity to glucocorticoid in chronic obstructive pulmonary disease (chronic obstructive pulmonary) is related to the intranuclear metastasis of glucocorticoids receptor gr 伪. Methods Human peripheral blood mononuclear cells (PBMCs) from 15 patients with mild and moderate asthma and 15 patients with COPD were cultured in vitro and their IL-8 protein levels were detected by Elisa. The semi-inhibitory concentration of dexamethasone (Dex). PBMCs were cultured in Dex for 6 hours. The intranuclear transfer of gr 伪 protein level was detected by Western blot, and the intranuclear transfer of gr 伪 was observed and evaluated by immunofluorescence and confocal microscopy. Results compared with mild and moderate asthma patients with COPD and healthy volunteers, the relative insensitivity of PBMC to Dex. Dex semi-inhibitory rate (IC50Dex) was negatively correlated with the intranuclear transfer of glucocorticoid receptor gr 伪 (r-0.54 PnP 0.0008). Dex could induce the increase of total gr 伪 in PBMC, but the intracellular distribution of gr 伪 was increased. There was significant difference between the groups. Dex could significantly increase the gr 伪 in the nucleus of healthy subjects and asthmatic patients, but did not increase the nuclear gr 伪 of the patients with COPD. Dex pretreatment in PBMC of healthy subjects and asthmatic patients significantly inhibited TNF- 伪 -induced IL-8 secretion, but not in PBMC of COPD patients. Conclusion the insensitivity of COPD to glucocorticoid may be one of the reasons why glucocorticoid plays a poor role in inhibiting inflammation in COPD patients.
【作者单位】：复旦大学附属中山医院呼吸科;浙江大学医学院附属第二医院感染科;复旦大学附属中山医院实验研究中心;
【基金】：国家自然科学基金(81270078,81470211)~~
【分类号】：R563.9

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