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[1]刘一鹏,欧宗兴*,陈忠仁,等.NLRP3炎性小体对慢性阻塞性肺疾病大鼠肺功能及炎性因子分泌的影响[J].厦门大学学报(自然科学版),2019,58(04):526-531.[doi:10.6043/j.issn.0438-0479.201808014]
 LIU Yipeng,OU Zongxing*,CHEN Zhongren,et al.Influence of NLRP3 inflammasome on lung function and inflammatory cytokines secretion in chronic obstructive pulmonary disease rats[J].Journal of Xiamen University(Natural Science),2019,58(04):526-531.[doi:10.6043/j.issn.0438-0479.201808014]
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NLRP3炎性小体对慢性阻塞性肺疾病大鼠肺功能及炎性因子分泌的影响(PDF)
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《厦门大学学报(自然科学版)》[ISSN:0438-0479/CN:35-1070/N]

卷:
58卷
期数:
2019年04期
页码:
526-531
栏目:
研究论文
出版日期:
2019-07-28

文章信息/Info

Title:
Influence of NLRP3 inflammasome on lung function and inflammatory cytokines secretion in chronic obstructive pulmonary disease rats
文章编号:
0438-0479(2019)04-0526-06
作者:
刘一鹏欧宗兴*陈忠仁王 蕾沈 彬梁海梅
中南大学湘雅医学院附属海口医院呼吸内科,海南 海口 570208
Author(s):
LIU YipengOU Zongxing*CHEN ZhongrenWANG LeiSHEN BinLIANG Haimei
Department of Respiratory Medicine,Central South University Xiangya School of Medicine Affiliated Haikou Hospital,Haikou 570208,China
关键词:
慢性阻塞性肺疾病 NLRP3炎性小体 白细胞介素-18 白细胞介素-1β 肺功能
Keywords:
chronic obstructive pulmonary disease NLRP3 inflammasome IL-18 IL-1β lung function
分类号:
R 563.3
DOI:
10.6043/j.issn.0438-0479.201808014
文献标志码:
A
摘要:
为了探讨核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎性小体在慢性阻塞性肺疾病(COPD)发病中的作用,并分析白细胞介素-18(IL-18)及白细胞介素-1β(IL-1β)在COPD大鼠体内分泌与肺功能的关系,按照随机原则将36只wistar大鼠平均分为空白组、COPD组及干预组,其中COPD组及干预组建造大鼠模型,干预组在造模的同时给予AC-YVAD-CMK抑制剂处理,造模结束后测定3组大鼠的呼吸阻力、肺总量、肺顺应性及血清、支气管肺泡灌洗液(BALF)中IL-18和IL-1β的水平.结果显示:1)COPD组大鼠的肺总量和肺顺应性均低于干预组和空白组(p<0.05),呼吸阻力大小依次为COPD组>干预组>空白组(p<0.05); 2)COPD组大鼠血清中IL-1β水平高于空白组和干预组(p<0.05),COPD组和干预组大鼠血清中IL-18水平高于空白组(p<0.05); 3)COPD组大鼠BALF中 IL-18水平高于干预组和空白组(p<0.05),BALF中IL-1β水平大小依次为COPD组>干预组>空白组(p<0.05); 4)大鼠BALF中IL-18水平与其呼吸阻力呈显著正相关(p<0.05).由上述结果可知:COPD模型大鼠的肺总量、肺顺应性降低而呼吸阻力升高,体内IL-18和IL-1β水平升高,且BALF中IL-18水平与大鼠呼吸阻力呈正相关性,提示IL-18参与了COPD炎症反应; 阻断NLRP3炎性小体中caspase-1活化可以改善COPD模型大鼠肺功能并降低IL-18和IL-1β水平,提示NLRP3炎性小体可能参与了大鼠COPD的发病过程.
Abstract:
To investigate the pathogenesis of leotide-binding oligomerization domain-1ike receptors family pyrin domain containing 3(NLRP3)inflammasome of chronic obstructive pulmonary disease(COPD)as well as to explore the relationship between the secretion of IL-18,IL-1β in COPD rats and lung function, we randomized 36 wistar rats into three groups:the control group, the COPD group and the intervention group,and built the COPD rat models.The intervention group was given AC-YVAD-CMK inhibitor at the same time as building. Respiratory resistance(Rrs), total lung capacity(TLC),lung compliance(Crs),IL-18 and IL-1β levels in serum and broncho-alveolar lavage fluid(BALF)were determined after building.Results showed as following:1)The TLC and Crs of COPD group were lower than those in the intervention group and the control group(p<0.05),and the decreasing order in the levels of Rrs were the COPD group,the intervention group and the control group(p<0.05).2)IL-1β level in serum of rats in the COPD group were higher than that in the control group and the intervention group,and the IL-18 level in serum of the COPD group and the intervention group was higher than that in the control group(p<0.05).3)The IL-18 level in BALF of the COPD group was higher than that in the intervention group and the control group.The IL-1β level in BALF of the three groups was the greatest in the COPD group,followed by the intervention group and then the control group,and all of difference were significant(p<0.05).4)Rrs showed significant positive correlation with the IL-18 level in BALF.Taken together,the TLC and Crs decreased in the COPD model rats,but Rrs,IL-18 and IL-1β levels increased,and the IL-18 level in BLAF of rats was correlated with the Rrs,which indicated that IL-18 was involved in the inflammatory response in COPD.Moreover,the lung function might be improved, and IL-18 and IL-1β levels might decreased in COPD rats by inhibition of caspase-1 activation in NLRP3 inflammasome,which indicated that NLRP3 inflammasome was involved in the pathogenesis of COPD rats.

参考文献/References:

[1] 蔡柏蔷,李龙芸.协和呼吸病学[M].2版.北京:中国协和医科大学出版社,2011:1077.
[2] BARNES P J,SHAPIRO S D,PAUWELS R A.Chronic obstructive pulmonary disease: molecular and cellularmecha-nisms[J].European Respiratory Journal,2003,14(2):672-688.
[3] MARTINON F,BURNS K,TSCHOPP J.The inflamma-some:a molecular platform triggering activation of inflammatory caspases and processing of proIL-β[J].Molecular Cell,2002,10(2):417-426.
[4] ELLIOTT E I,SUTTERWALA F S.Initiation and perpetuation of NLRP3 inflammasome activation and assembly[J].Immunological Reviews,2015,265(1):35-52.
[5] 宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型的建立及药物干预的影响[J].中华内科杂志,2000,39(8):556-557.
[6] SOZEN T,TSUCHIYAMA R,HASEGAWA Y,et al. Role of interleukin-1β in early brain injury after subarachnoid hemorrhage in mice[J].Stroke,2009,40(7):2519.
[7] 刘莹,董文鹏,陈长富,等.Caspase-1抑制剂在野百合碱诱导的肺动脉高压大鼠中的作用[J].广东医学,2017,38(23):3566-3570.
[8] 刘一鹏.抑制NLRP3炎性小体对COPD大鼠IL-18、IL-1β及肺功能的影响[D].长沙:中南大学,2018:6-7.
[9] MUNESWARAO J,VERMA A K,HASSALI M A A.Global initiative for chronic obstructive lung disease(GOLD)2018 report:highlighting an incorrect information[J].Pulmonary Pharmacology & Therapeutics,2017,49:10.
[10] HAASKEN S,SUTTERWALA F S.Damage control:management of cellular stress by the NLRP3 inflamma-some[J].European Journal of Immunology,2013,43(8):2003-2005.
[11] DINARELLO C A,SIMON A,VAN DER MEER J W.Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases[J].Nat Rev Drug Discov,2012,11(8):633-652.
[12] FURUTATE R,ISHII T,MOTEGI T,et al.The neutrophil to lymphocyte ratio is related to disease severity and exacerbation in patients with chronic obstructive pulmonary disease[J].Internal Medicine,2016,55(3):223.
[13] KITASATO Y,HOSHINO T, OKAMOTO M, et al. Enhanced expression of interleukin-18 and its receptor in idiopathic pulmonary fibrosis[J].American Journal of Respiratory Cell & Molecular Biology,2004,31(6):619-625.
[14] ROVINA N,DIMA E,GERASSIMOU C,et al.Interleukin-1 in induced sputum:association with lung function chronic obstructive pulmonary disease[J].Respir Med, 2009,103(7):1056-1062.
[15] DE NAROO D,DE NAROO C M,LATZ E.New insights into mechanisms controlling theNLRP3 inflammasome and its role in lung disease[J].The American Journal of Pathology,2014,184(1):42-54.
[16] SATOH T,OTSUKA A,CONTASSOT E,et al. The inflammasome and IL-1β:implications for the treatment of inflammatory diseases[J].Immunotherapy,2015,7(3):243-254.
[17] KRATZER A,SALYS J,NOLD-PETRY C,et al.Role of IL-18 in second-hand smoke-induced emphysema[J].American Journal of Respiratory Cell & Molecular Biology,2013,48(6):725-732.

备注/Memo

备注/Memo:
收稿日期:2018-08-22录用日期:2018-11-26
基金项目:海南省自然科学基金(2017817386)
*通信作者:ouzongxing@163.com
更新日期/Last Update: 1900-01-01