间歇性高容量血液滤过对严重脓毒症患者Toll样受体2表达及预后的影响

Influence of pulse high volume hemofiltration on toll-like receptor 2 expression and prognosis in patients with severe sepsis

目的探讨应用间歇性高容量血液滤过(PHVHF)后,严重脓毒症患者外周血单核细胞Toll样受体2(TLR2)mRNA表达水平变化及预后情况。方法将40例严重脓毒症患者分为PHVHF组(20例)和常规治疗组(20例),在相同的常规治疗基础上,PHVHF组加用PHVHF治疗,至少持续治疗72h。于治疗前后比较两组患者急性病生理学和长期健康评价(APACHE)Ⅱ评分和序贯器官功能衰竭(SOFA)评分;并记录两组患者28d生存率和重症监护病房(ICU)住院时间。采用酶联免疫吸附测定法检测治疗前及治疗后24、48、72h各时间点血浆中肿瘤坏死因子α(TNF-α)和白细胞介素10(IL-10)浓度,同时以半定量逆转录聚合酶链技术检测TLR2mRNA表达。结果两组患者治疗前APACHEⅡ评分、SOFA评分、TLR2mRNA、TNF-α、IL-10水平的差异均无统计学意义(P均>0.05)。治疗后PHVHF组患者APACHEⅡ、SOFA评分均下降(P均<0.05)。两组患者28d生存率差异无统计学意义(P>0.05),但PHVHF组ICU住院时间短于常规治疗组(P<0.05)。治疗72h后,PHVHF组患者血浆TNF-α、IL-10、TLR2mRNA表达水平较治疗前明显下降(P均<0.05),与同期常规治疗组比较,差异均有统计学意义(P均<0.05);PHVHF组血浆IL-10/TNF-α比值也较常规治疗组显著升高(P<0.05)。结论 PHVHF能通过清除炎症介质,下调外周血单核细胞表面TLR2表达,达到恢复机体促炎/抗炎平衡,从而改善严重脓毒症患者的总体病情。

Objective To investigate the effect of pulse high volume hemofiltration （PHVHF） on the expression of toll-like receptor 2 （TLR2） and prognosis in patients with severe sepsis. Methods Forty patients with severe sepsis were divided into PHVHF group （20 cases） and control group （20 cases） randomly. The patients in the control group were treated with conventional therapy, and the patients in the PHVHF group received at least 72 h of PHVHF treatment additionly. The acute physiology and chronic health evaluation （APACHE）Ⅱ score, the sequential organ failure assessment （SOFA） score, the 28-day survival rate and intensive care unit （ICU） length of stay were recorded and compared. The levels of tumor necrosis factor-alpha （TNF-α） and interleukin-10 （IL-10） were detected by enzyme linked immunosorbent assay, and the TLR2 mRNA expression in peripheral blood mononuclear cells （PBMC） were measured by semi-quantitative reverse transcriptase polymerase chain reaction analysis before and at 24, 48, 72 h after the treatment. Results There were no significant differences in the APACHEⅡ and SOFA scores, the level of plasma TNF-α, IL-10 and TLR2 mRNA between the two groups before the treatment （all P〈0.05）. And the APACHEⅡ and SOFA scores descreased markedly in the PHVHF group after the treatment （all P〈0.05）. The ICU length of stay in the PHVHF group was all longer （P〈0.05）, while the 28-day survival rate showed no significant difference when compared to the controls （90% vs. 70%, P〈0.05）. In the PHVHF group, the levels of TNF-α, IL-10 and TLR2 mRNA were decreased apparently at 72 h after the treatment （all P〈0.05）, and those indexes were lower than the control group （all P〈0.05）. Meanwhile, the ratio of IL-10 / TNF-α in the PHVHF group was higher than the control group （P〈0.05）. Conclusion PHVHF can eliminate inflammatory mediators, decrease the expression of TLR2 in PBMC and thereby bring pro-inflammatory and anti-inflammatory states into balance in patients with serve sepsis.