脓毒血症患者外周血单个核细胞中TLR4/MyD88/NF-κB通路与疾病严重程度的关系

Relationship between TLR4/MyD88/NF-κB Pathway in Peripheral Blood Mononuclear Cells and Severity of Sepsis

目的探究脓毒血症患者外周血单个核细胞中Toll样受体4(TLR4)/髓样分化因子88(MyD88)/核因子κB(NF-κB)信号通路与疾病严重程度的关系。方法选取2018年11月至2020年10月河北北方学院附属第一医院收治的102例脓毒血症患者作为病例组,根据患者病情严重程度分为脓毒症亚组[急性生理学和慢性健康状况评价Ⅱ(APACHEⅡ)评分0~10分,42例]、严重脓毒症亚组(APACHEⅡ评分11~20分,34例)、脓毒症休克组(APACHEⅡ评分>20分,26例),纳入同期100名健康体检者作为对照组。采用二喹啉甲酸法测定TLR4、NF-κB、MyD88蛋白水平,比较病例组和对照组及不同病情严重程度患者上述蛋白表达水平。采用Pearson分析上述相关因子水平与脓毒血症患者疾病严重程度的关系。结果入院时病例组TLR4、NF-κB、MyD88表达水平高于对照组(7.1±1.7比1.0±0.4;7.3±1.8比1.0±0.4;18.2±3.2比8.3±2.0)(P<0.01)。各亚组治疗后的TLR4、MyD88、NF-κB均低于治疗前(P<0.05);治疗前和治疗后,严重脓毒症亚组和脓毒症休克组TLR4、NF-κB、MyD88表达均明显高于脓毒症亚组(P<0.05),脓毒症休克组TLR4、NF-κB、MyD88表达均明显高于严重脓毒症亚组(P<0.05)。Pearson相关性分析结果显示,脓毒血症患者入院时外周血单核细胞中TLR4、MyD88、NF-κB与APACHEⅡ均呈正相关(r=0.328,P=0.012;r=0.650,P<0.001;r=0.569,P<0.001),且与SOFA评分呈正相关(r=0.384,P=0.017;r=0.623,P<0.001;r=0.540,P<0.001)。结论脓毒血症患者TLR4、NF-κB、MyD88表达异常,且不同严重程度的脓毒血症患者上述相关因子表达亦呈现明显差异。检测TLR4、NF-κB、MyD88有助于评估脓毒血症患者病情,对临床科学治疗有指导作用。

Objective To explore the relationship between Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway in peripheral blood mononuclear cells of patients with sepsis and the disease severity.Methods A total of 102 patients with sepsis admitted to the First Affiliated Hospital of Hebei North University from Nov.2018 to Oct.2020 were included as a case group,and were further divided into a sepsis subgroup[acute physiology and chronic health evaluationⅡ(APACHEⅡ)score 0-10,42 cases],a severe sepsis subgroup(APACHEⅡscore 11-20,34 cases),and a sepsis shock group(APACHEⅡscore>20,26 cases),while 100 healthy individuals of physical examination in the same period were includedas a control group.The protein concentrations of TLR4,NF-κB and MyD88 were detected by diquinoline formic acid method,the expression levels of the above proteins among the case group,the control group,and different subgroups were compared.Pearson analysis was used to investigate the relationship between the levels of the aforementioned factors and the disease severity of septic patients.Results At admission,the expression levels of TLR4,NF-κB and MyD88 in the case group were higher than those in the control group(7.1±1.7 vs 1.0±0.4,7.3±1.8 vs 1.0±0.4,18.2±3.2 vs 8.3±2.0)(P<0.01).The levels of TLR4,MyD88 and NF-κB after treatment of each subgroup were lower than those before treatment(P<0.05).Before and after treatment,the expressions of TLR4,NF-κB and MyD88 in the severe sepsis subgroup and septic shock group were significantly higher than those in the sepsis subgroup(P<0.05),and the expressions of TLR4,NF-κB and MyD88 in septic shock group were significantly higher than those in the severe sepsis subgroup(P<0.05).Pearson correlation analysis showed that TLR4,MyD88,NF-κB in peripheral blood mononuclear cells of patients with sepsis were all positively correlated with APACHEⅡ(r=0.328,P=0.012;r=0.650,P<0.001;r=0.569,P<0.001),and was positively correlated with SOFA score(r=0.384,P=0.017;r=0.623,P<0.001;r=0.540,P<0.001).Conclusion The expression levels of TLR4,NF-κB and MyD88 in septic patients are abnormal,and there are significant differences in the expression of the above factors among septic patients in different subtype groups.It can help to assess the condition of septic patients and provide guidance for the scientific clinical treatment by detection of TLR4,NF-κB and MyD88.