| 摘要: |
| 目的探讨平常固有免疫中核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）炎症小体通路在慢性阻塞性肺病（COPD）发展中的作用。方法选取94例COPD患者为研究对象，中度、重度、极重度分别31、33和30例。采集急性加重期和稳定期的外周血标本，采用荧光定量PCR检测外周血NLRP3、接头蛋白凋亡相关点样蛋白（ASC）、半胱天冬酶1（Caspase-1）、IL-1β、IL-18mRNA表达水平，采用ELISA法测定血清细胞因子IL-1β、IL-18浓度；并在稳定期测定肺功能，分析稳定期外周血炎症小体成分及下游分子mRNA表达水平与肺功能指标的相关性。结果不论是稳定期或急性加重期，重度、极重度组外周血NLRP3、ASC、Caspase-1、IL-1β、IL-18mRNA表达水平均明显高于中度组（均P＜0.05），极重度组又明显高于重度组（均P＜0.05）；与稳定期比较，3组患者急性加重期均明显升高（均P＜0.05）。不论是稳定期或急性加重期，重度、极重度组血清IL-1β、IL-18浓度均明显高于中度组（均P＜0.05），极重度组又明显高于重度组（均P＜0.05）；与稳定期比较，3组患者急性加重期均明显升高（均P＜0.05）。稳定期COPD患者外周血炎症小体成分及下游分子mRNA表达水平与FEV1占预计值、FEV1/FVC均呈负相关（均P＜0.01）。结论NLRP3炎症小体通路可能参与COPD反复急性加重、肺功能进行性下降的过程，与COPD进展密切相关。 |
| 关键词: 慢性阻塞性肺病 炎症小体 核苷酸结合寡聚化结构域样受体蛋白 3 接头蛋白凋亡相关点样蛋白 半胱天冬酶 1
肺功能 |
| DOI：10.12056/j.issn.1006-2785.2017.39.01.2016-1344 |
| 分类号: |
| 基金项目:宁波市自然科学基金项目（2013A610237） |
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| Association of NLRP3 inflammasome signaling pathway with progression of chronic obstructive pulmonary disease |
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WANG Shi, WANG Huaying, WENG Yuesong, LAN Pengxun, JIANG Hao, YU Wanjun, YING Kejing
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Zhejiang University School of Medicine
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| Abstract: |
| Objective To study the association of NLR pyrin domain-containing protein 3 (NLRP3) inflammasome signaling pathway with the progression of chronic obstructive pulmonary disease (COPD). Methods Ninety four COPD patients, including 31 cases of stage Ⅱ (moderate), 33 cases of stage Ⅲ (severe) and 30 cases of stage Ⅳ (extremely severe), were enrolled in the study. The pulmonary function was examined in patients both with stable and acute exacerbation stages. The expression of NLRP3, ASC, Casp-1, IL-1β, IL-18 mRNA in peripheral blood mononuclear cells (PBMCs) were determined by
real-time PCR. The concentrations of cytokines IL-1β and IL-18 in serum were measured by ELISA. The correlation between the levels of NLRP3, ASC, Casp-1, IL-1β, IL-18 mRNA and pulmonary function was evaluated. Results Significantly higher levels of NLRP3, ASC, Casp-1, IL-1β, IL-18 mRNA transcripts in PBMC from severe and extremely severe COPD groups were found both in the stable and acute exacerbation stage COPD patients, compared with moderate COPD group (all P＜0.05). And the above indexes in extremely severe COPD group were higher than those in severe COPD patients (all P＜0.05). Significantly higher levels of NLRP3, ASC, Casp-1, IL-1β, IL-18 mRNA transcripts in PBMC from acute exacerbation stage COPD patients were also found in moderate, severe and extremely Severe COPD groups compared with stable stages COPD group patients (all P＜ 0.05). Higher serum IL-1β and IL-18 levels in severe and extremely severe COPD groups were found both in the stable and acute exacerbation stage COPD patients compared with moderate COPD group (all P＜0.05). And the IL-1β and IL-18 levels in extremely severe COPD group were higher than those in severe COPD group (both P＜0.05). Higher serum levels of IL-1β and
IL-18 levels from acute exacerbation stage COPD patients were also found in moderate, severe and extremely Severe COPD groups compared with stable stages COPD group patients (all P＜0.05). The increased levels of NLRP3, ASC, Casp-1, IL-1β,
IL-18 mRNA transcripts in PBMC were negatively correlated with the values of FEV1, and FEV1/FVC in stable stages COPD group patients (all P＜0.01). Conclusion NLRP3 inflammasome activation is associated with the acute exacerbation and deterioration of pulmonary function and involved in the progression of COPD. |
| Key words: Chronic obstructive pulmonary disease Inflammasome NLRP3 ASC Caspase-1 Pulmonary function |
