[1]杨文林,顾慧玲,倪红燕,等.慢性阻塞性肺疾病(COPD)模型大鼠肺组织中NLRP3炎症小体表达水平的变化及意义[J].现代检验医学杂志,2018,33(06):69-72.[doi:10.3969/j.issn.1671-7414.2018.06.018]
　YANG Wen-lin,GU Hui-ling,NI Hong-yan,et al.Changes and Significance of NLRP3 Inflammasome in the Rats Model of Chronic Obstructive Pulmonary Disease(COPD)[J].Journal of Modern Laboratory Medicine,2018,33(06):69-72.[doi:10.3969/j.issn.1671-7414.2018.06.018]
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慢性阻塞性肺疾病(COPD)模型大鼠肺组织中NLRP3炎症小体表达水平的变化及意义()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第33卷
期数:
2018年06期
页码:
69-72
栏目:
论著
出版日期:
2018-12-24

文章信息/Info

Title:
Changes and Significance of NLRP3 Inflammasome in the Rats Model of Chronic Obstructive Pulmonary Disease(COPD)
文章编号:
1671-7414(2018)06-069-04
作者:
杨文林; 顾慧玲; 倪红燕; 王海峰
上海市第一人民医院宝山分院呼吸科,上海 200940
Author(s):
YANG Wen-lin; GU Hui-ling; NI Hong-yan; WANG Hai-feng
Department of Respiratory,Baoshan Branch of Shanghai First People's Hospital,Shanghai 200940,China
关键词:
NOD样受体热蛋白结构域相关蛋白3炎症小体;  慢性阻塞性肺疾病;  大鼠COPD模型
分类号:
R563; R-332
DOI:
10.3969/j.issn.1671-7414.2018.06.018
文献标志码:
A
摘要:
目的 探讨NOD样受体热蛋白结构相关蛋白3(NLRP3)炎症小体在慢性阻塞性肺疾病(COPD)模型中的变化及意义。方法 将30只雄性大鼠随机分为2组,正常对照组(n=10只)给予自由饮水和摄食,喂养75天; 吸烟组(n=20只)采用单纯吸入香烟烟雾的方法制造大鼠COPD模型,连续75天后再根据大鼠最大呼气流速(PEF)及气道肺组织病理变化分为吸烟COPD组(n=9只)和吸烟非COPD组(n=11只)。收集支气管肺泡灌洗液(BALF)计算巨噬细胞(AMC)、中性粒细胞(NEU)和淋巴细胞(LYM)的绝对计数。采用酶联免疫吸附试验(ELISA)、逆转录-聚合酶链反应(RT-PCR)技术分别测定BALF,肺组织中NLRP3炎症小体的浓度以及NLRP3 mRNA的相对表达量。结果与正常对照组比较,吸烟非COPD组、吸烟COPD组BALF中NEU(×106/L)(524.2±73.1,916.9±84.8 vs 106.6±31.8),AMC(×106/L)(1 570.9±273.5,2 307.8±410.4 vs 496.6±61.7)和LYM(×106/L)(72.1±14.7,115.4±23.8 vs 21.6±4.2),计数明显升高,吸烟COPD组BALF中NEU,AMC和LYM计数亦较吸烟非COPD组明显升高(F=350.59,100.57,82.63,均P<0.05)。与正常对照组比较,吸烟非COPD组、吸烟COPD组BALF(pg/ml)(107.8±23.5,126.7±34.9 vs 76.7±15.1),肺组织(pg/ml)(118.8±33.3,147.4±40.2 vs 84.1±21.5)中NLRP3炎症小体的浓度明显升高,与吸烟非COPD组比较,吸烟COPD组BALF,肺组织中NLRP3炎症小体的浓度亦明显升高(F=9.53,9.17,均P<0.05)。吸烟非COPD组和吸烟COPD组肺组织NLRP3 mRNA相对表达量均显著高于正常对照组(P<0.05),吸烟COPD组肺组织NLRP3 mRNA相对表达量显著高于吸烟非COPD组(P<0.05)。BALF,肺组织中NLRP3炎症小体浓度、肺组织NLRP3 mRNA相对表达量与NEU,AMC,LYM计数均呈显著正相关(P<0.05)。结论 NLRP3炎症小体参与了COPD慢性炎症的发生、发展,与肺组织炎症细胞以及气道病理改变密切相关,阻断NLRP3炎性小体的活化,有望成为治疗COPD新的靶点和方向。
Abstract:
Objective To explore the changes and significance of NLRP3 inflammasome in the rats of chronic obstructive pulmonary disease(COPD).Methods 30 male rats were divided randomly into twogroups.Control group(n=10)was given with drink and eat freely for 75 days.Smoking group(n=20)was given with inhaling cigarette smoke to establishrat model of COPD.After 75 days,the rats in smoking group were divided into smoking COPD group(n=9)and smoking non-COPD group(n=11)according to the maximum expiratory velocity(PEF)and pathologic changes of airway lung tissue.Bronchoalveolar lavage fluid(BALF)was collected to calculate the count of macrophages(AMC),neutrophils(NEU),and lymphocyte(LYM).Enzyme-linked immunosorbent(ELISA),reverse transcription-polymerase chain reaction(RT-PCR)wasused to detect the NLRP3 inflammasome in BALF and lung tissue,and the relativeexpression of NLRP3mRNA.Results Compared with control group,the count of NEU(×106/L)(524.2±73.1,916.9±84.8 vs 106.6±31.8),AMC(×106/L)(1 570.9±273.5,2 307.8±410.4 vs 496.6±61.7)and LYM(×106/L)(72.1±14.7,115.4±23.8 vs 21.6±4.2)in BALF of smoking COPD group and smoking non-COPD group were increased significantly,these indicatorswere also increased significantly in smoking COPD group compared with smoking non-COPD groups(F=350.59,100.57 and 82.63,all P<0.05).Compared with control group,the count of NEU,AMC,LYM in BALF of smoking COPD group and smoking non-COPD group were increased significantly,these indicators were also increased significantly in smoking COPD group compared with smoking non-COPDgroups(P<0.05).Compared with control group,the concentration of NLRP3 inflammasome in BALF(pg/ml)(107.8±23.5,126.7±34.9 vs 76.7±15.1),lungtissue(118.8±33.3 pg/ml,147.4±40.2 pg/ml vs 84.1±21.5 pg/ml)of smoking COPD group and smoking non-COPD group was increased significantly,and these indicators were also increased significantly in smoking COPD group comparedwith smoking non-COPD groups(F=9.53,9.17,all P<0.05).The NLRP3 mRNA relative expression in lung tissue of smoking COPD group and smoking non-COPD group was significantly lower than that of control group,and the NLRP3 mRNArelative expression in lung tissue of smoking COPD group was significantly lowerthan that of smoking non-COPD group(P<0.05).The concentration of NLRP3inflammasome in BALF,lung tissue,and NLRP3mRNA relative expression in lung tissue were significantly positive correlated with NEU,AMC and LYM count(P<0.05).Conclusion NLRP3 inflammasome involves in the occurrence and development of chronic inflammation of COPD,and closely related withinflammation cells of lung tissue and airway pathologic change,blocking the activation of NLRP3 inflammasome is expected to be as a new target and direction in the treatment of COPD.

参考文献/References:

[1] Global strategy for the diagnosis,management,and prevention ofchronic obstructive pulmonary disease(Updated 2014)[EB/OL].http://www.goldcopd.org/Global Initiative for Chronic Obstructive Lung Distase.
[2] Crim C,Dransfield MT,Bourbeau J,et al.Pneumonia risk with inhaled fluticasone furoate and vilanterol compared with vilanterol alone in patients withCOPD[J].Ann Am Thorac Soc,2015,12(1):27-34.
[3] Zheng F,Xing SS,Gong ZS,et al.Silence of NLRP3 suppresses atherosclerosis and stabilizes plaques in apolipoprotein E-deficient mice[J]. MediatorsInflamm,2014,2014(1):507208.
[4] Wang HY,L(¨overu)C,Wang S,et al.NLRP3 inflammasome involves in theacute exacerbation of patients with chronic obstructive pulmonary disease[J].Inflammation,2018,11(6):1-13.
[5] 谢圆媛,杨丹芬.老年COPD患者外周血单核细胞TLR2,TLR4的表达及其与炎症因子的关系研究[J].现代检验医学杂志,2015,30(4):80-83,86.
Xie YY,Yang DF.Study on the expressions of TLR2,TLR4 in peripheral blood mononuclear cells and its correlation with the inflammatory factors levels of the elderly patients with COPD[J].Journal of Modern Laboratory Medicine,2015,30(4):80-83,86.
[6] Howrylak JA,Nakahira K.Inflammasomes:key mediators of lung immunity[J].Annu Rev Physiol,2017,79(12):471-494.
[7] Faner R,Sobradillo P,Noguera A,et al.The inflammasome pathway in stable COPD and acute exacerbations[J].ERJ Open Res,2016,2(3):2010-2016.
[8] Di Stefano A,Caramori G,Barczyk A,et al.Innate immunity but not NLRP3inflammasome activation correlates with severity of stable COPD[J].Thorax,2014,69(6):516-524.
[9] 马 强,吴占庆,杨培雄,等.慢性阻塞性肺疾病患者血清白细胞介素表达及临床意义[J].中国老年学杂志,2016,36(17):4266-4267.
Ma Q,Wu ZQ,Yang PX,et al.Expression and clinical significanceofinterleukin in patients with chronic obstructive pulmonary disease[J].ChineseJournal of Gerontology,2016,36(17):4266-4267.
[10] Mankan AK,Dau T,Jenne D,et al.The NLRP3/ASC/Caspase-1 axisregulates IL-1β processing in neutrophils[J].Eur J Immunol,2012,42(3):710-715.
[11] 冯 一,陈 丽,李 红,等.FIZZ1在吸烟大鼠COPD模型肺组织的表达及与气道炎症的相关性研究[J].中国病理生理杂志,2018,34(6):1101-1108.
Feng Y,Chen L,Li H,et al.Expression of FIZZ1 on lung tissue of cigarette smoking-induced COPD rats and its relationship with airway inflammation[J].Chinese Journal of Pathophysiology,2018,34(6):1101-1105.
[12] 钟琳晔,杨 汀.NLRP3炎症小体及其激活产物在慢性阻塞性肺疾病中的作用研究进展[J].国际呼吸杂志,2013,33(15):1182-1187.
Zhong LY,Yang T.Research advance of the role of the NLRP3 inflammasome and its products in the pathogenesis of chronic obstructive pulmonary disease[J].Int J Respir,2013,33(15):1182-1187.
[13] Faustin B,Reed JC.Reconstituting the NLRP1 inflammasome in vitro[J].Methods Mol Biol,2013,1040(12):137-152.
[14] Coll RC,Robertson AA,Chae JJ.A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases[J].Nat Med,2015,21(3):248-255.
[15] Westwell-Roper C,Dunne A,Kim ML,et al.Activating the NLRP3 inflammasome using the amyloidogenic peptide IAPP[J].Methods Mol Biol,2013,1040(2):9-18.

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备注/Memo

备注/Memo:
基金项目:上海市宝山区科学技术委员会(编号:14-E-12)。
作者简介:杨文林(1968-),男,本科,副主任医师,研究方向:哮喘,肺部感染,肺癌等,E-mail:yangwen19684@sina.com。
更新日期/Last Update: 2018-11-30