脓毒症患者连续性肾脏替代治疗后Toll样受体4的改变

The change in expression of Toll -like receptor 4 on peripheral blood mononuclear cell after continuous renal replacement therapy in patients with sepsis

目的观察脓毒症患者外周血单核细胞（PBMC）Toll样受体4（TLR4）及下游炎症介质的表达变化，以及持续性血液透析治疗对其调控的作用。方法13例脓毒症患者按预后分为好转组（7例）和治愈组（6例），另选6例健康志愿者为正常对照组。采用逆转录-聚合酶链反应（RT—PCR）方法检测PBMC中TLR4 mRNA的表达；用流式细胞仪检测PBMC表面TLR4的表达；用酶联免疫吸附法（ELISA）检测血清中自细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）的浓度。结果经过高容量血液滤过（HVHF）的连续性肾脏替代治疗（CRRT）以及其他综合治疗后，13例患者的血清IL-6和TNF-α明显降低（P均〈0．05），临床症状趋向好转，且治愈组低于好转组，并接近正常对照组水平；同时TLR4的表达也有所降低，但其降低幅度滞后于IL-6和TNF-α的降低幅度，在好转期仍有高水平的TLR4表达。结论CRRT所导致的单核细胞TLR4降低可能在脓毒症患者的治疗中具有重要的意义。

Objective To explore the change in Toll - like receptor 4 （TLR4） of peripheral blood mononuclear cell （PBMC） and the expression of cytokines in patients with sepsis, and to investigate the role of continuous renal replacement therapy （CRRT） in its modution. Methods A clinical study was performed in 13 patients with sepsis which were divided into improved group （n= 7） and healing group （n： 6）, according to their outcome. Another 6 healthy individuals served as normal control. The mRNA expression of TLR4 on PBMC was detected by reverse transcription- polymerase chain reaction （RT-PCR）, the protein expression of TLR4 on PBMC was assayed with flow cytometry, the expressions of IL - 6 and TNF-α were measured by enzyme linked immunoadsorbent assay （ELISA）. Results TLR4 mRNA, IL - 6, TNF-α, and TLR4 protein expressions were upregulated markedly in patients suffering from sepsis. The above parameters were decreased significantly after CRRT （all P 〈0. 05） and in the same time, the clinic condition turn up, in the meanwhile, the expression of TLR4 went down, but it still have some expression on monocyte in improved group. Conclusion The down regulation of TLR4 through CRRT may imply an important mechanism in the CRRT on patients with sepsis.