脓毒症Toll样受体信号通路和细胞免疫炎症因子水平

目的分析脓毒症患者Toll样受体(TLRs)信号通路和细胞免疫炎症因子水平及临床意义。方法回顾性分析承德市中心医院收治的124例脓毒症患者的临床资料,根据其病情程度分为重症脓毒症组(重症组,28例)及非重症脓毒症组(非重症组,96例),并纳入38名同期健康体检者作为对照组。比较三组入院时TLRs信号传导途径分子TLR-2、TLR-4表达水平、外周血单核细胞(PBMC)表面核因子-κB(NF-κB)及外周血T淋巴细胞亚群(CD3+、CD4+/CD8+)、炎症因子C-反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)]差异,使用受试者工作特征(ROC)曲线评估上述指标对重症脓毒症的诊断价值。结果重症组糖尿病患病占比46.43%高于非重症组11.46%(P<0.001)。重症组入院时PBMC表面TLR-2、TLR-4、NF-κB表达水平及外周血CRP、TNF-α分别为(37.60±6.69)%、(17.46±4.71)%、(3.57±0.70)及(93.71±17.27)mg/L、(79.15±13.75)ng/L高于非重症组(25.02±4.86)%、(12.12±3.01)%、(2.86±0.55)及(70.68±15.00)mg/L、(60.82±12.11)ng/L及对照组(P<0.05),而非重症组上述指标均高于对照组(P<0.05);重症组入院时外周血CD3+、CD4+/CD8+分别为(45.54±11.58)%、(0.89±0.16)均低于非重症组(57.38±12.30)%、(1.37±0.30)及对照组(P<0.05),而非重症组低于对照组(P<0.05);入院时PBMC表面TLR-2、TLR-4、NF-κB表达水平及外周血CD3+、CD4+/CD8+、CRP、TNF-α水平均对重症脓毒症具有较高诊断价值(P<0.05)。非重症组临床疗效优于重症组(P<0.001);治疗5 d时,两组PBMC表面TLR-2、TLR-4、NF-κB表达水平及外周血CRP、TNF-α水平均较治疗前降低(P<0.05),且外周血CD3+、CD4+/CD8+水平较治疗前升高(P<0.05);重症组治疗前后PBMC表面TLR-2、TLR-4、NF-κB表达水平及外周血CRP、TNF-α水平均高于非重症组(P<0.05),外周血CD3+、CD4+/CD8+水平均低于非重症组(P<0.05)。结论 TLRs信号通路异常激活、免疫抑制、炎症反应强烈是脓毒症发生、发展的重要因素,积极监测相关指标对脓毒症诊疗有利。

Toll like receptor signaling pathway and cellular immune inflammatory factors with sepsis

OBJECTIVE To analyze the levels of Toll like receptors(TLRs) signaling pathway and cellular immune inflammatory factors in patients with sepsis and their clinical significance. METHODS The clinical data of 124 patients with sepsis in Chengde central hospital were retrospectively analyzed, and were divided into severe sepsis group(critical group, 28 cases) and non-severe sepsis group(non-sever disease group, 96 cases) according to the severity of sepsis, and 38 people who had physical examinations during the same period were included as control group. The differences in the expression levels of TLR-2 and TLR-4, nuclear factor-κB(NF-κB) of peripheral blood mononuclear cells(PBMC), T lymphocyte subsets(CD3+, CD4+/CD8+) and inflammatory factors C-reactive protein(CRP), tumor necrosis factor-α(TNF-α)] were compared among the three groups upon admission. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic value of the above indicators for severe sepsis. RESULTS Diabetes in the severe group accounted for 46.43%, which was significantly higher than that in non severe group(11.46%, P<0.001). The expression levels of TLR-2, TLR-4, NF-κB on the surface of PBMC, CRP and TNF-α in peripheral blood of severe group at admission were(37.60±6.69)%,(17.46±4.71)%,(3.57±0.70) and(93.71±17.27) mg/L, and(79.15±13.75) ng/L, respectively, significantly higher than those of non-severe group((25.02±4.86)%,(12.12±3.01)%,(2.86±0.55),(70.68±15.00) mg/L, and(60.82±12.11), respectively) and the control group(P<0.05), while the above indicators of the non-sever group were significantly higher than those of the control group(P<0.05). The peripheral blood CD3+and CD4+/CD8+ of patients at admission in the severe group were(45.54±11.58)% and(0.89±0.16) respectively, significantly lower than those in the non-severe group((57.38±12.30)% and(1.37±0.30), respectively) and the control group(P<0.05), while those in the non-severe group were significantly lower than those in the control group(P<0.05). ROC curve analysis showed that the expression level of TLR-2, TLR-4 and NF-κ B on the surface of PBMC and the levels of CD3+, CD4+/CD8+, CRP and TNF-α in peripheral blood at admission had a high diagnostic value for severe sepsis(P<0.05). The clinical efficacy of non-severe group was significantly better than that of severe group(P<0.001). On the 5 th day of treatment, the expression levels of TLR-2, TLR-4, NF-κ B on the surface of PBMC and the levels of CRP and TNF-α in peripheral blood of the two groups were significantly lower than those before treatment(P<0.05), and the levels of CD3+, CD4+/CD8+in peripheral blood of the two groups were significantly higher than those before treatment(P<0.05);the expression levels of TLR-2, TLR-4, NF-κ B on the surface of PBMC and the levels of CRP and TNF-α in peripheral blood of the severe group before and after treatment were significantly higher than those of the non-severe group(P<0.05), and the levels of CD3+, CD4+/CD8+ in peripheral blood of the severe group were significantly lower than those of the non-severe group(P<0.05). CONCLUSION Abnormal activation of TLRs signaling pathway, immunosuppression and strong inflammatory response are important factors for the occurrence and development of sepsis. Active monitoring of related indicators is beneficial to the diagnosis and treatment of sepsis.