高通量连续性血液滤过治疗对创伤脓毒症患者外周血单核细胞miRNA-146表达的影响  

Effect of high volume hemofiltration on miRNA-146 expression in peripheral blood mononuclearcells from patients with posttraumatic sepsis

作　　者：茅尧生[1] 李智鑫[1] 吕铁[1] 周蕾[1] 

机构地区：[1]绍兴市人民医院重症医学科,312000

出　　处：《中华创伤杂志》2013年第12期1215-1219,共5页Chinese Journal of Trauma

基　　金：绍兴市社会发展重点科研资助项目（2011A23021）

摘　　要：目的探讨高通量连续性血液滤过（high volume hemofiltration，HVHF）技术治疗对脓毒症患者外周血单核细胞miRNA-146表达的影响及治疗脓毒症的可能机制。方法选择符合纳入标准的创伤脓毒症患者25例，分入HVHF组；另选25例同样符合纳入标准的与HVHF组配对的性别相同、年龄和急性生理和慢性健康评分（APACHE）-Ⅱ相近但因某些原因未能行HVHF治疗而其余治疗措施相同的创伤脓毒症患者作为对照组。两组患者治疗过程在0，6，12，24，48h时，分离外周血单核细胞，检测其miRNA-146表达量的变化。将治疗24h后的两组患者分离外周血单核细胞，于体外培养，以脂多糖（1ipopolysaccharide，LPS）刺激4，8，12，24，48h时，检测单核细胞中miRNA-146表达量的变化；同时用ELISA法检测单核细胞培养液中TNF—a、IL-6、IL-10水平。结果（1）随着治疗的进行，HVHF组miRNA-146表达量较脓毒症组下调更显著；（2）HVHF组在孵育前及孵育后4，8h时，miRNA-146表达明显低于同时相点的脓毒症组，其单核细胞接受LPS再刺激后对炎症反应能力也较脓毒症组强。结论HVHF治疗对创伤脓毒症患者免疫功能有一定的恢复作用，可明显改善患者的预后。而HVHF治疗可通过间接下调单核细胞miRNA-146的表达水平，减轻其对单核细胞炎症因子释放的抑制作用，增强其对外界再刺激的反应能力，可能为其治疗机制之一。Objective To investigate the effect of high volume hemofiltration （HVHF） on expression of miRNA-146 in peripheral blood mononuclear cells in posttraumatic sepsis patients and its therapeutic mechanism. Methods Twenty-five cases of posttraumatic sepsis were included as HVHF group. Another 25 age-and gender-matched traumatic sepsis patients with similar APACHE-II who received no HVHF treatment for some reasons were used as controls. Therapeutic measurements were the same of the two groups except for HVHF. At 0-, 6-, 12-, 24- and 48-hour time points, the peripheral blood mononuclear cells were isolated from patients of both groups to detect level of miRNA-146. Peripheral blood mononuclear cells isolated at 24 hours were incubated with lipopolysaccharide （LPS） in vitro. At hours 4, 8, 12, 24 and 48 after incubation, level of miRNA-146 in mononuclear cells was determined and levels of TNF-α, IL-6, and IL-10 in the substrate was detected by ELISA. Results （ 1 ） Level of miRNA-146 in HVHF group was decreased significantly over time as compared with that in sepsis group; （2） Before incubation and at 4-and 8-hour after incubation, miRNA-146 level was lowered significantly in HVHF group as compared with that in sepsis group. After LPS stimulation, mononuclear cell also presented a stronger inflammatory response in HVHF group than in sepsis group. Conclusions HVHF provides a definite effect on immune function recovery and a significant improvement in prognosis. Moreover, HVHF may attenuate the impact of miRNA-146 on mononuclear cell inflammatory factor release and en- hance the cell ability to respond to external stimuli again via down-regulating miRNA-146, as may be one of the therapeutic mechanisms of HVHF for posttraumatic sepsis.

关 键 词：脓毒症 血液滤过 单核细胞 miRNA-146 

分 类 号：R459.7[医药卫生—急诊医学]