基于Toll样受体4/核因子-κB信号通路探究血液灌流联合血液滤过对脓毒症诱导的血管内皮组织炎性损伤的作用机制

Probing the mechanism of Toll-like receptor 4/nuclear factor-kappa B signaling pathway-based action of hemoperfusion combined with hemofiltration on sepsis-induced inflammatory injury in vascular endothelial tissue

目的探讨血液灌流联合血液滤过对脓毒症患者Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路相关因子水平的影响。方法回顾性选取2020年2月至2023年2月在菏泽市立医院治疗的150例脓毒症患者为研究对象,根据治疗方案的不同分为对照组和观察组,各75例。两组均予以脓毒症标准治疗,于此基础上,对照组予以血液滤过治疗,观察组予以血液灌流联合血液滤过治疗。比较两组治疗前、治疗后72 h TLR4/NF-κB信号通路相关mRNA表达(TLR4 mRNA、NF-κB mRNA)及相关炎性因子、血管内皮功能相关指标、肝肾功能指标水平,并比较两组28 d病死率。结果相较于治疗前,两组治疗后72 h TLR4 mRNA及NF-κB mRNA明显下降,观察组低于对照组(0.34±0.12比0.63±0.16、0.30±0.10比0.59±0.12),差异均有统计学意义(P<0.05)。相较于治疗前,两组治疗后72 h肿瘤坏死因子-α、白细胞介素(IL)-6、IL-12及C反应蛋白水平均下降,观察组低于对照组[(43.42±7.82)ng/L比(56.37±9.41)ng/L、(28.47±6.03)ng/L比(39.41±7.02)ng/L、(52.31±5.42)ng/L比(70.84±7.08)ng/L、(23.82±7.06)mg/L比(38.41±6.83)mg/L],差异有统计学意义(P<0.05)。相较于治疗前,两组治疗后72 h晚期糖基化终产物、可溶性细胞间黏附因子-1、同型半胱氨酸、丙氨酸氨基转氨酶、天冬氨酸氨基转移酶、血尿素氮及血肌酐明显下降,观察组低于对照组[(172.37±73.63)mg/L比(249.41±80.26)mg/L、(404.26±68.42)ng/L比(459.36±70.19)ng/L、(20.27±4.53)μmol/L比(28.96±5.02)μmol/L、(62.41±10.69)U/L比(78.52±13.41)U/L、(51.47±12.35)U/L比(64.17±15.83)U/L、(3.82±0.79)mmol/L比(5.57±1.16)mmol/L、(125.16±23.96)μmol/L比(163.24±30.12)μmol/L],差异均有统计学意义(P<0.05)。观察组28 d病死率低于对照组[12.00%(9/75)比25.33%(19/75)],差异有统计学意义(χ^(2)=4.39,P<0.05)。结论血液灌流联合血液滤过治疗脓毒症可有效缓解病情程度,减轻肝肾功能损伤,对TLR4/NF-κB信号通路相关mRNA表达及相关炎性因子均有一定作用。

Objective To explore the mechanism of hemoperfusion combined with hemofiltration in the treatment of sepsis based on Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.Methods One hundred and fifty patients with sepsis treated in the Heze Municipal Hospital from February 2020 to February 2023 were retrospectively selected and they were divided into two groups according to the treatment plan,with 75 cases in each group.Both groups were treated with standard treatment for sepsis,with hemofiltration in the control group and hemoperfusion combined with hemofiltration in the observation group.The TLR4/NF-κB signal pathway-related mRNA expression(TLR4 mRNA,NF-κB mRNA),related inflammatory factors,indicators of vascular endothelial function,the levels of indicators of liver and kidney function were measured between the two groups.The 28-d morbidity and mortality rate was compared between the two groups.Results Compared with before treatment,the levels of TLR4 mRNA,NF-κB mRNA in two groups were decreased,and the levels of above index in the observation group were lower than those in the control group:0.34±0.12 vs.0.63±0.16,0.30±0.10 vs.0.59±0.12,there were statistical differences(P<0.05).Compared with before treatment,the levels of tumour necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-12 and C reactive protein(CRP)in two groups were decreased,and the levels of above index in the observation group were lower than those in the control group:(43.42±7.82)ng/L vs.(56.37±9.41)ng/L,(28.47±6.03)ng/L vs.(39.41±7.02)ng/L,(52.31±5.42)ng/L vs.(70.84±7.08)ng/L,(23.82±7.06)mg/L vs.(38.41±6.83)mg/L,there were statistical differences(P<0.05).Compared with before treatment,the levels of advanced glycosylation end products(AGEs),soluble intercellular adhesion factor-1(sICAM-1),homocysteine(Hcy),glutamate transaminase(ALT),glutathione transaminase(AST),blood creatinine(Scr)and blood urea nitrogen(BUN)in two groups were decreased,and the levels of above index in the observation group were lower than those in the control group:(172.37±73.63)mg/L vs.(249.41±80.26)mg/L,(404.26±68.42)ng/L vs.(459.36±70.19)ng/L,(20.27±4.53)μmol/L vs.(28.96±5.02)μmol/L,(62.41±10.69)U/L vs.(78.52±13.41)U/L,(51.47±12.35)U/L vs.(64.17±15.83)U/L,(3.82±0.79)mmol/L vs.(5.57±1.16)mmol/L,(125.16±23.96)μmol/L vs.(163.24±30.12)μmol/L,there were statistical differences(P<0.05).The 28-d morbidity and mortality rate in the observation group was lower than that in the control group:12.00%(9/75)vs.25.33%(19/75),there was statistical difference(χ^(2)=4.39,P<0.05).Conclusions In the treatment of sepsis,hemoperfusion combined with hemofiltration can effectively alleviate the severity of the disease,reduce the damage of hepatic and renal function,and have a certain effect on the mRNA expression of TLR4/NF-κB signaling pathway and related inflammatory factors.