Toll样受体2、4/MyD88/NF-κB信号通路及相关分子在COPD发病机制中的作用及临床意义

The role and clinical significance of Toll like receptor 2,4/MyD88/NF-κB signaling pathway and related molecules in the pathogenesis of COPD

目的探讨Toll样受体2、4/MyD88/NF-κB信号通路及相关分子在慢性阻塞性肺疾病(COPD)发病机制中的作用及临床意义。方法选取2017年1月~2018年12月南充市中心医院呼吸内科治疗的112例COPD患者为研究对象,根据疾病进展分为急性加重期组(n=52)与稳定期组(n=60),并选取同时段于该院健康体检者为对照组(n=68)。应用实时荧光定量PCR法检测3组外周血单个核细胞(PBMC)中TLR2、TLR4、MyD88、NF-κB mRNA表达水平,采用ELISA法检测3组血清中IL-1β、IL-10、TNF-α、CRP及sICAM-1等炎性因子表达水平。选取急性加重期患者外周血进行全血培养,分别用生理盐水(NS)、脂多糖(LPS)、LPS+TLR4Ab、肽聚糖(PNG)、PNG+TLR2Ab处理,检测PBMC中mRNA及血清炎性因子表达水平。结果急性加重期组患者TLR2、TLR4、MyD88、NF-κB mRNA水平及血清中IL-1β、IL-10、TNF-α、CRP、sICAM-1等炎性因子显著高于稳定期组和对照组,稳定期组患者各mRNA水平及血清炎性因子水平高于对照组(均P<0.05)。NS对照组的各mRNA水平及血清炎性因子水平显著低于其他4组(均P<0.05);单独经LPS处理后各mRNA水平及血清炎性因子显著增加,且经过LPS+TLR4Ab处理后,各mRNA水平及血清炎性因子显著降低(均P<0.05);单独经PNG处理后各mRNA水平及血清炎性因子显著增加,经PNG+TLR2Ab处理后各mRNA水平及血清炎性因子显著降低(均P<0.05)。结论COPD患者外周血单核细胞Toll样受体2、4/MyD88/NF-κB信号通路处于活化状态,可促进下游炎性因子释放,参与COPD炎症过程。

Objective To study the role and clinical significance of Toll like receptor 2,4/MyD88/NF-κB signaling pathway and related molecules in the pathogenesis of COPD.Methods 112 COPD outpatients were treated with respiratory medicine in our hospital from January 2017 to December 2018,and were divided into observation group(52 cases)and control group(60 cases)according to the progress of the disease.The patients with physical examination in our hospital were selected for the control group(68cases)at the same time.The expression levels of TLR2,TLR4,MyD88 and NF-κB mRNA in PBMC of three groups were detected by real-time fluorescent quantitative PCR,and the expression levels of IL-1β,IL-10,TNF-α,CRP and sICAM-1 in serum of three groups were detected by ELISA.The peripheral blood of patients with AECOPD was cultured with normal saline,LPS,LPS+TLR4Ab,PNG,PNG+TLR2Ab,respectively.The expression of mRNA in PBMC and serum inflammatory factors was detected.Results The levels of TLR2,TLR4,MyD88,NF-κB mRNA,and serum IL-1β,IL-10,TNF-α,CRP,and sICAM-1 in patients with acute exacerbation were significantly higher than those in stable and control group(P<0.05).The levels of mRNA and serum inflammatory factors in the stable group were higher than those in the control group(P<0.05).The levels of mRNA and serum inflammatory factors in NS control group were significantly lower than those in other 4 groups(P<0.05).After LPS treatment alone,all mRNA levels and serum inflammatory factors increased significantly(P<0.05).After LPS+TLR4Ab treatment,each mRNA level and serum inflammatory factors were significantly reduced(P<0.05);After PNG treatment alone,all mRNA levels and serum inflammatory factors were significantly increased(P<0.05).After treatment with PNG+TLR2Ab,all mRNA levels and serum inflammatory factors were significantly reduced(P<0.05).Conclusion The activation of Toll-like receptor 2,4/MyD88/NF-B signal pathway in peripheral blood of patients with COPD can increase the release of the downstream inflammatory factors and participate in the inflammatory process of COPD.