脓毒症合并心肌损伤患者TLR4/NF-κB信号通路及其与心肌损伤标志物的相关性

TLR4/NF-κB signaling pathway and its correlation with markers of myocardial injury in patients with sepsis complicated with myocardial injury

目的探讨脓毒症合并心肌损伤患者Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路与心肌损伤标志物的相关性。方法回顾性选取2020年6月至2022年6月应急管理部应急总医院收治的脓毒症患者84例作为研究对象,根据患者有无心肌损伤分为无心肌损伤组(n=59)和心肌损伤组(n=25)。以酶联免疫吸附试验法检测血清脑钠肽(BNP)、N末端B型脑钠肽(NT-proBNP)、人心型脂肪酸结合蛋白(h-FABP)、心肌肌钙蛋白Ⅰ(cTnⅠ)、肌酸激酶同工酶(CK-MB);以实时荧光定量PCR法检测外周血单个核细胞(PBMC)中TLR4、NF-κB、MyD88 mRNA相对表达量。比较两组血清BNP、NT-proBNP、h-FABP、cTnⅠ、CK-MB水平,以及PBMC中TLR4、NF-κB、MyD88 mRNA相对表达量。以Pearson相关系数分析血清BNP、NT-proBNP、h-FABP、cTnⅠ、CK-MB水平与TLR4、NF-κB、MyD88相对表达量的相关性。结果心肌损伤组血清BNP、NT-proBNP、h-FABP、cTnⅠ、CK-MB水平分别为(442.17±85.06)ng/L、(2306.94±417.39)pg/mL、(16.09±3.17)μg/L、(0.43±0.11)μg/L、(11.47±3.75)μg/mL,均高于无心肌损伤组[(374.39±51.82)ng/L、(418.52±112.64)pg/mL、(13.27±3.84)μg/L、(0.24±0.07)μg/L、(2.16±0.41)μg/mL],差异均有统计学意义(P<0.05)。心肌损伤组TLR4、NF-κB、MyD88 mRNA相对表达量分别为2.73±0.42、2.33±0.38、1.94±0.47,均高于无心肌损伤组(1.68±0.35、1.49±0.24、1.22±0.29),差异均有统计学意义(P<0.05)。经相关性分析,血清BNP、NT-proBNP、h-FABP、cTnⅠ、CK-MB水平与TLR4、NF-κB、MyD88 mRNA相对表达量呈正相关(P<0.05)。结论脓毒症合并心肌损伤患者血清BNP、NT-proBNP、h-FABP、cTnⅠ、CK-MB等标志物水平出现明显升高,其机制可能与TLR4/NF-κB信号通路的激活有关。

Objective To investigate the correlation between Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) signaling pathway and markers of myocardial injury in patients with sepsis complicated with myocardial injury.Methods A total of 84 patients with sepsis admitted to Emergency General Hospital of Emergency Management from June 2020 to June 2022 were retrospectively selected as the study subjects,and they were divided into no myocardial injury group(n=59) and myocardial injury group(n=25) according to whether the patients had myocardial injury or not.Serum brain natriuretic peptide(BNP),N-terminal B-type brain natriuretic peptide(NT-proBNP),human fatty acid binding protein(h-FABP),cardiac troponin Ⅰ(cTnⅠ) and creatine kinase isoenzyme(CK-MB) were detected by enzyme-linked immunosorbent assay.The relative expression levels of TLR4,NF-κB and MyD88 mRNA of peripheral blood mononuclear cell were detected by real time fluorogenic quantitative PCR.The levels of serum BNP,NT proBNP,h-FABP,cTnⅠ,CK-MB,as well as TLR4,NF-κB,MyD88 in PBMC of two groups were compared.The relative expression levels of MyD88 mRNA were compared.The correlation between the levels of BNP,NT-proBNP,h-FABP,cTnⅠ and CK-MB and the relative expression levels of TLR4,NF-κB and MyD88 in serum was analyzed by Pearson correlation coefficient.Results The levels of serum BNP,NT-proBNP,h-FABP,cTnⅠ and CK-MB in myocardial injury group were(442.17±85.06) ng/L,(2 306.94±417.39) pg/mL,(16.09±3.17) μg/L,(0.43±0.11) μg/L,and(11.47±3.75) μg/mL,respectively,which were higher than those in the no myocardial injury group[(374.39±51.82) ng/L,(418.52±112.64) pg/mL,(13.27±3.84) μg/L,(0.24±0.07) μg/L,(2.16±0.41) μg/mL],the differences were statistically significant(P<0.05).the relative expressions of TLR4,NF-κB and MyD88 mRNA in myocardium injury group were 2.73±0.42,2.33±0.38 and 1.94±0.47,respectively,which were higher than those in the no myocardial injury group(1.68±0.35,1.49±0.24 and 1.22±0.29),the differences were statistically significant(P<0.05).Correlation analysis showed that the levels of serum BNP,NT-proBNP,h-FABP,cTnⅠ and CK-MB were positively correlated with the relative expression levels of TLR4,NF-κB and MyD88 mRNA(P<0.05).Conclusion Serum levels of BNP,NT-proBNP,h-FABP,cTnⅠ,CK-MB were significantly increased in patients with sepsis complicated with myocardial injury,the mechanism of which may be related to the activation of TLR4/NF-κB signaling pathway.