乌司他丁辅助治疗对脓毒症患者炎症细胞亚群及分泌细胞因子的影响

The effect of ulinastatin on inflammatory cells and secreting cytokines in patients with sepsis

目的:观察脓毒症患者外周血炎症细胞和细胞因子的变化,并观察乌司他丁辅助治疗对脓毒症患者炎症细胞和细胞因子表达的影响。方法:选择2014-09-2016-10入住我院重症医学科的脓毒症患者53例,分为常规治疗组(29例,给予常规集束化治疗)和乌司他丁治疗组(24例,在常规治疗基础上给予乌司他丁30万IU/次静脉注射,3次/d),于治疗前和治疗7d后采集外周血,并选择15例年龄和性别比例相匹配的健康志愿者作为对照组,检测辅助性T细胞(CD3+CD4+)、杀伤性T细胞(CD3+CD8+)、自然杀伤细胞(NK细胞,CD3-CD56+)以及12种细胞因子的水平,观察乌司他丁的干预作用。结果:辅助性T细胞和杀伤性T细胞水平在脓毒症组和对照组之间差异无统计学意义,而脓毒症组中NK细胞的水平较对照组明显升高[(11.33±5.15)%vs.(11.33±5.15)%,P=0.040]。血清中IL-6和IL-8在脓毒症患者中的水平显著高于对照组(P<0.05),而IL-10水平在脓毒症患者血清中显著降低(P<0.05),余细胞因子未检出或在两组间表达差异无统计学意义。治疗前NK细胞的比例,IL-6、IL-8以及IL-10的水平在常规治疗组和乌司他丁治疗组之间差异无统计学意义,乌司他丁治疗辅助治疗后IL-6和IL-8的水平较常规治疗组显著下降(P<0.05),而治疗后IL-10在常规治疗组和乌司他丁治疗组比较差异无统计学意义。结论:乌司他丁治疗可有效降低脓毒症患者NK细胞水平,下调IL-6和IL-8异常升高表达,在脓毒症治疗中发挥免疫调控作用,有望改善脓毒症患者的预后。

Objective：To observe the changes of peripheral inflammatory cells and cytokines in patients with sepsis,and to investigate the effect of ulinsatatin on inflammatory cells and secreting cytokines.Method：A total of fifty-three patients with sepsis who were admitted to intensive care unit during September 2014 to October 2016 were enrolled.The patients were divided into two groups：routine treatment group（n=29,received routine bundle therapies）and ulinastatin treatment group（n=24,received 30 kIU ulinastatin three times daily in addition to routine bundle therapies）.Blood samples were collected before and after 7days of treatments.Meanwhile,fifteen healthy individuals with matched age and sex ratio were also collected as normal controls（NCs）.T helper cells（Th cells,CD3＋CD4＋）,cytotoxic T cells（CTLs,CD3＋CD8＋）,natural killer cells（NK cells,CD3-CD56＋）,and twelve cytokines were determined in order to observe the effect of ulinastatin.Result：There were no significant differences of Th cells and CTLs between NCs and patients with sepsis.However,the percentage of NK cells was remarkably increased in sepsis than in NCs[（11.33±5.15）% vs.（11.33±5.15）%,P=0.040].Moreover,expressions of IL-6and IL-8were notably elevated in the serum isolated from sepsis patients（P〈0.05）.In contrast,IL-10 concentration was significantly reduced in sepsis patients（P〈0.05）.Other cytokines levels were either undetectable or failed to achieve significances.There were no significant differences in IL-6,IL-8,and IL-10 levels between routine treatment group and ulinastatin treatment group before therapy.Ulinastatin therapy significantly reduced the expression of IL-6and IL-8in comparison with routine treatment group（P〈0.05）,however,IL-10 expression did not reduced significantly in response to ulinastatin therapy.Conclusion：Ulinastatin therapy effectively reduced the NK cells and down-regulated IL-6/IL-8expression in patients with sepsis.Ulinastatin might play an immunomodulatory role,and might expected to improve the prognosis of patients with sepsis.