中国呼吸与危重监护杂志

中国呼吸与危重监护杂志

NLRP3 炎性小体在慢性阻塞性肺疾病患者机体炎症反应中作用的研究

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目的 研究 NOD 样受体热蛋白结构域相关蛋白 3(NLRP3) 炎性小体及其下游炎症因子在慢性阻塞性肺疾病(简称慢阻肺)患者和健康人之间表达的差异,揭示 NLRP3 炎性小体在慢阻肺发病机制中的可能作用。 方法 选取 2016 年 11 月至 2017 年 5 月住院的 40 例慢阻肺患者纳入急性加重期组,其经过治疗进入稳定期后纳入稳定期组,选取 40 例健康体检者纳入对照组。采集各组一般资料和外周血,荧光定量 PCR 法测定外周血单个核细胞中 NLRP3 mRNA 水平,酶联免疫法检测血浆白细胞介素-18(IL-18)和白细胞介素-1β(IL-1β)水平。 结果 急性加重期组慢阻肺患者的 NLRP3 mRNA、IL-18 和 IL-1β 水平显著高于稳定期组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml 比1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml,P<0.05]。急性加重期组慢阻肺患者的 NLRP3 mRNA、IL-18 和 IL-1β 水平显著高于对照组[2.11±0.77,12.79(7.10,43.13)pg/ml,17.02(8.36,52.21)pg/ml比 1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。稳定期组慢阻肺患者的 NLRP3 mRNA 、IL-18 和 IL-1β 水平显著高于对照组 [1.60±0.44,10.66(6.32,18.59)pg/ml,13.34(7.07,16.89)pg/ml 比 1.00±0.49,6.29(4.73,7.93)pg/ml,5.93(4.81,9.67)pg/ml,P<0.05]。急性加重期组血浆 IL-18 水平和白细胞计数、中性粒细胞百分比呈正相关 (r=0.372,P<0.05;r=0.386,P<0.05);急性加重期组 NLRP3 mRNA 表达量和稳定期组 NLRP3 mRNA 表达量均与 CAT 评分正相关(r=0.387,P<0.05;r=0.399,P<0.05)。 结论 NLRP3 炎性小体参与慢阻肺患者的机体炎症反应。

Objective To study the expression of NLRP3 inflammasome and its downstream inflammatory factors in patients with chronic obstructive pulmonary disease (COPD) and healthy controls, and to reveal the effect and significance of NLRP3 inflammasome in the pathogenesis of COPD. Methods Forty patients with acute exacerbation COPD (AECOPD) who were hospitalized from November 2016 to May 2017 were recruited in the AECOPD group, and recruited in the stable COPD group when they entered the stable stage. Forty healthy individuals were recruited in the control group. General information and peripheral blood were collected from each subject. The levels of NLRP3 mRNA and caspase-1 mRNA in peripheral blood mononuclear cells were measured by real-time PCR. The levels of IL-18 and IL-1β were measured by enzyme-linked immunosorbent assay. Results The levels of NLRP3 mRNA, IL-18 and IL-1β in the AECOPD patients were significantly higher than those in the stable COPD group [2.11±0.77, 12.79 (7.10, 43.13) pg/ml, 17.02 (8.36, 52.21) pg/ml vs. 1.60±0.44, 10.66 (6.32, 18.59) pg/ml, 13.34 (7.07, 16.89) pg/ml, all P<0.05] . The levels of NLRP3 mRNA, IL-18 and IL-1β in the AECOPD patients were significantly higher than those in the control group [2.11±0.77, 12.79 (7.10, 43.13) pg/ml, 17.02 (8.36, 52.21) pg/mlvs. 1.00±0.49, 6.29 (4.73, 7.93) pg/ml, 5.93 (4.81, 9.67) pg/ml, all P<0.05]. The levels of NLRP3 mRNA, IL-18 and IL-1β were significantly higher in the stable COPD group than the control group [1.60±0.44, 10.66 (6.32, 18.59) pg/ml, 13.34 (7.07, 16.89) pg/mlvs. (1.00±0.49, 6.29 (4.73, 7.93) pg/ml, 5.93 (4.81, 9.67) pg/ml, all P<0.05]. Correlation analysis showed that the plasma IL-18 level was positive correlated with leukocyte count and neutrophil percentage in the AECOPD group (r=0.372, P<0.05;r=0.386, P<0.05). The expression of NLRP3 mRNA in the AECOPD group and stable COPD group were positively correlated with the CAT score (r=0.387, P<0.05;r=0.399, P<0.05) . Conclusion NLRP3 inflammasome is involved in the inflammatory response in COPD patients.

关键词: 慢性阻塞性肺疾病; NLRP3 炎性小体; IL-18; IL-1β; 外周血单个核细胞

Key words: Chronic obstructive pulmonary disease; NLRP3 inflammasome; IL-18; IL-1β; Peripheral blood mononuclear cells

引用本文: 何子凡, 高岩, 王晓玲, 许西琳, 刘冬, 卢献灵. NLRP3 炎性小体在慢性阻塞性肺疾病患者机体炎症反应中作用的研究. 中国呼吸与危重监护杂志, 2018, 17(2): 119-123. doi: 10.7507/1671-6205.201707043 复制

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