下呼吸道细菌定植对稳定期COPD患者TLR2/NF-κB信号通路、免疫功能及气道重塑的影响  

Effect of lower respiratory bacterial colonization on TLR2/NF-κB signaling pathways, immune function and airway remodeling in patients with stable COPD

作　　者：王春侠[1] 董万里[1] 范娜 刘洋 冯冬冬[1] 门琤 WANG Chun-xia;DONG Wan-li;FAN Na;LIU Yang;FENG Dong-dong;MEN Cheng(Nanyang Central Hospital,Nanyang,Henan 473009,China)

机构地区：[1]南阳市中心医院呼吸与危重症医学科一病区,河南南阳473009

出　　处：《中华医院感染学杂志》2022年第7期966-970,共5页Chinese Journal of Nosocomiology

基　　金：南阳市科技局科技攻关基金资助项目(KJGG193)。

摘　　要：目的探讨下呼吸道细菌定植对稳定期慢性阻塞性肺疾病(COPD)患者Toll样受体2(TLR2)/核转录因子-κB(NF-κB)信号通路、免疫功能及气道重塑的影响。方法选取2018年6月-2020年6月南阳市中心医院收治的稳定期COPD患者102例,根据患者痰培养细菌定植结果分为细菌定植组和细菌未定植组,比较两组患者肺功能[用力肺活量(FVC)、第1秒用力呼气容积(FEV_(1))、FEV_(1)%预计值(FEV_(1)%)、1秒率(FEV_(1)/FVC)]、血气指标[氧分压(PaO_(2))、动脉二氧化碳分压(PaCO_(2))、氧合指数(PaO_(2)/FiO_(2))]、免疫功能[CD_(3)^(+)、CD_(4)^(+)、CD_(8)^(+)、CD_(4)^(+)/CD_(8)^(+)]和血清炎性因子[C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)、白细胞介素-8(IL-8)]、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、基质金属蛋白酶组织抑制剂(TIMP-1)水平,采用聚合酶链式反应(PCR)检测外周血单个核细胞中TLR2和NF-κB mRNA水平。结果细菌定植组FEV_(1)、FEV_(1)%、FEV_(1)/FVC、PaO_(2)、PaO_(2)/FiO_(2)、CD_(3)^(+)、CD_(4)^(+)和CD_(4)^(+)/CD_(8)^(+)均低于细菌未定植组(P<0.05),而PaCO_(2)、WBC、CRP、TNF-α、IL-6、IL-8、MMP-9、MMP-2、TIMP-1、TLR2、NF-κB mRNA相对水平均高于细菌未定植组(P<0.05)。结论稳定期COPD患者下呼吸道细菌定植会降低患者机体免疫功能,提高机体炎症反应和气道重塑,影响患者肺功能,可能与提高TLR2/NF-κB信号通路活性存在关系。OBJECTIVE To explore the effect of lower respiratory bacterial colonization on Toll-like receptor 2(TLR2)/nuclear transcription factor-κB(NF-κB)signaling pathways,immune function and airway remodeling in patients with stable chronic obstructive pulmonary disease(COPD).METHODS A total of 102 patients with stable COPD admitted to Nanyang Central Hospital between Jun 2018 and Jun 2020 were enrolled.According to the results of bacterial colonization in sputum culture of patients,they were divided into the colonization group and non-colonization group.The levels of pulmonary function[including forced vital capacity(FVC),forced expiratory volume in 1 second(FEV_(1)),FEV_(1)%as percentage of predicted value(FEV_(1)%),(FEV_(1)/FVC)],blood gas indexes[including partial pressure of oxygen(PaO_(2)),partial pressure of carbon dioxide(PaCO_(2)),oxygenation index(PaO_(2)/FiO_(2))],immune function[including CD_(3)^(+),CD_(4)^(+),CD_(8)^(+),CD_(4)^(+)/CD_(8)^(+)percentages],serum inflammatory factors[including C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),interleukin-8(IL-8)],matrix metalloproteinase-2(MMP-2),matrix metalloproteinase-9(MMP-9)and tissue inhibitor of matrix metalloproteinase-1(TIMP-1)were compared between the two groups.The levels of TLR2 and NF-κB mRNA in peripheral blood mononuclear cells(PBMC)were detected by polymerase chain reaction(PCR).RESULTS Levels of FEV_(1),FEV_(1)%,FEV_(1)/FVC,PaO_(2),PaO_(2)/FiO_(2),CD_(3)^(+),CD_(4)^(+)and CD_(4)^(+)/CD_(8)^(+) in the colonization group were significantly lower than those in the non-colonization group(P<0.05),while PaCO_(2),WBC,CRP,TNF-α,IL-6,IL-8,MMP-9,MMP-2 and TIMP-1 levels,and relative mRNA expression levels of TLR2 and NF-κB were significantly higher than those in the non-colonization group(P<0.05).CONCLUSION The lower respiratory bacterial colonization will reduce immunal function of patients with stable COPD,increase inflammatory response and airway remodeling,leading to pulmonary function.It may be related to the increasing

关 键 词：慢性阻塞性肺疾病 稳定期 下呼吸道 细菌定植 气道重塑 免疫功能 TOLL样受体2 核转录因子-κB 

分 类 号：R563[医药卫生—呼吸系统]