氧化应激介导NLRP3炎性反应小体对慢性阻塞性肺疾病的影响研究

doi:10.3969/j.issn.1006-7795.2020.01.025

摘要/Abstract

摘要： 目的通过对慢性阻塞性肺疾病（chronic obstructive pulmonary disease，COPD）患者血清中氧化应激指标超氧化物歧化酶（superoxide dismutase，SOD）、丙二醛（malondialdehyde，MDA）浓度以及核苷酸结合寡聚化结构域样受体蛋白3（nucleotide binding oligomerization domain like receptor protein 3，NLRP3） mRNA的表达量的检测，分析NLRP3、MDA、SOD、第1秒用力呼气容积占预计值百分比（forced expiratory volume in the first second% pred，FEV1% pred）之间的相关性，从而探讨氧化应激介导NLRP3炎性小体活化对COPD的影响。方法选取2017年6月至2018年6月长沙市第一医院收治的COPD患者90例，其中慢性阻塞性肺疾病急性加重期（acute chronic obstructive pulmonary disease，AECOPD）患者60名，AECOPD组患者根据肺功能分为重-极重组和轻-中组，每组30例，经治疗症状体征达到缓解期水平的COPD稳定期患者30名，另选取同期体检健康者30例作为对照组。比较AECOPD组、COPD稳定期组、对照组血清中MDA、SOD浓度、NLRP3 mRNA表达量与COPD患者血清中MDA和SOD浓度、外周血淋巴细胞NLRP3 mRNA表达量、FEV1% pred之间的相关性采用Pearson相关性分析。结果血清中MDA浓度AECOPD组高于COPD稳定期组、COPD稳定期组高于健康对照组（P<0.05）；血清中SOD浓度AECOPD组低于COPD稳定期组、COPD稳定期组低于健康对照组（P<0.05）；外周血淋巴细胞中NLRP3 mRNA表达量AECOPD组高于COPD稳定期组、COPD稳定期组高于健康对照组（P<0.05）。AECOPD组血清中MDA浓度重-极重组高于轻-中组、轻-中组高于对照组（P<0.05）；AECOPD组血清中SOD浓度重-极重组低于轻-中组、轻-中组低于对照组（P<0.05）；AECOPD组外周血淋巴细胞NLRP3 mRNA表达量重-极重组高于轻-中组、轻-中组高于对照组（P<0.05）。Pearson相关性分析结果显示，COPD患者中血清MDA浓度与NLRP3 mRNA表达量呈正相关（r=0.64，P<0.05）；COPD患者中血清SOD浓度与NLRP3 mRNA表达量呈负相关（r=-0.90，P<0.05）；COPD患者FEV1% pred与NLRP3 mRNA表达量呈负相关（r=-0.78，P<0.05）。结论氧化应激和NLRP3炎性反应小体参与COPD发病过程，氧化应激和NLRP3 mRNA表达量升高与COPD病情加重相关，氧化应激介导NLRP3炎性小体活化对COPD疾病进展有影响。

关键词: 氧化应激, NLRP3炎性反应小体, 慢性阻塞性肺疾病

Abstract: Objective The correlation among nucleotide binding oligomerization domain like receptor protein 3(NLRP3), malondialdehyde(MDA), superoxide dismutase(SOD) and forced expiratory volume in the first second% pred(FEV1% pred) was analyzed by detecting the levels of SOD, MDA and the expression level of NLRP3 mRNA in serum of COPD patients, so as to explore the influence of oxidative stress-mediated NLRP3 inflammatory body activation on COPD. Methods Selection of Changsha's Hospitals affiliated to Nanhua University in June 2017 to June 2018, 90 cases of COPD patients including 60 patients with acute chronic obstructive pulmonary disease (AECOPD).According to pulmonary function in patients with AECOPD group is divided into weight very restructuring and light-medium group, 30 cases in each group.Selected 30 COPD patients who reached the level remission after treatment symptoms and selected the other 30 cases who got healthy subjects through physical examination as a control group.Serum MDA, SOD levels and NLRP3 mRNA expression levels in AECOPD group, COPD stable period group, control group were compared. Otherwise, serum MDA, SOD levels and NLRP3 mRNA expression levels in weight-very restructuring group, light-medium group and healthy control group were compared.Pearson correlation analysis was used to analyze the correlation between serum MDA and SOD levels, NLRP3 mRNA expression in peripheral blood lymphocytes, and FEV1% pred in COPD patients.Results Serum MDA level in AECOPD group was higher than that in COPD stable period group and COPD stable period group was higher than that in healthy control group (P<0.05). Serum SOD level in AECOPD group was lower than that in COPD stable period group and COPD stable period group was lower than that in healthy control group (P<0.05).The expression level of NLRP3 mRNA in peripheral blood lymphocytes in AECOPD group was higher than that in COPD stable period group and COPD stable period group was higher than that in healthy control group (P<0.05). Serum MDA level in the weight-very restructuring group was higher than that in the light-medium group and the light-medium group was higher than that in the healthy control group (P<0.05). Serum MDA level in the weight-very restructuring group was lower than that in light-medium group and light-medium group was lower than that in the healthy control group (P<0.05). The expression level of NLRP3 mRNA in peripheral blood lymphocytes in weight-very restructuring group was significantly higher than that in the light-medium group and the light-medium group was higher than that in the healthy control group (P<0.05). The result of pearson correlation analysis showed that serum MDA level in COPD patients was positively correlated with NLRP3 mRNA expression, with a correlation coefficient r of 0.64(P<0.05). Serum SOD level was negatively correlated with NLRP3 mRNA expression in COPD patients, with a correlation coefficient r of -0.90(P<0.05). In COPD patients, FEV1%pred was negatively correlated with NLRP3 mRNA expression, and the correlation coefficient r was -0.78 (P<0.05). Conclusion Oxidative stress and NLRP3 inflammatory corpuscle are involved in the pathogenesis of COPD. The increasing of oxidative stress and NLRP3 mRNA expression were correlated with exacerbations of COPD. Oxidative stress-mediated activation of NLRP3 inflammatory corpuscle has an impact on the progression of COPD.

Key words: oxidative stress, NLRP3 inflammasome, chronic obstructive pulmonary disease(COPD)

中图分类号:

R681

刘萍, 娄可, 文隆, 李慧, 汤渝玲. 氧化应激介导NLRP3炎性反应小体对慢性阻塞性肺疾病的影响研究[J]. 首都医科大学学报, 2020, 41(1): 131-136.

Liu Ping, Lou Ke, Weng Long, Li Hui, Tang Yuling. Oxidative stress mediates the effect of NLRP3 inflammasome on chronic obstructive pulmonary disease[J]. Journal of Capital Medical University, 2020, 41(1): 131-136.

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