目的 探讨肝移植患者在脓毒症不同阶段免疫状态的变化特点。方法选取2009年1月至2010年12月中山大学附属第三医院外科监护室收治的脓毒症患者47例作为研究对象,根据是否行肝移植手术和脓毒症状态分成肝移植脓毒症组(TS组, 11例)、肝移植严重脓毒症组(TSS组, 10例)、非肝移植脓毒症组(NTS组, 15例)、非肝移植严重脓毒症组(NTSS组, 11例),另选取20名健康人作为对照组。分别检测外周血TNF-α、IL-4、IL-10、IFN-γ和高迁移率蛋白B1(HMGB1)mRNA的水平,并记录4组患者急性生理学及慢性健康状况评分Ⅱ(APACHEⅡ)、SOFA评分以及28 d病死率。其中TSS组患者停用免疫抑制药物并给予免疫调理措施。结果TSS组和NTSS组APACHEⅡ评分、SOFA评分均高于TS和NTS组(P均< 0.01),TSS组SOFA评分明显高于NTSS组(P均< 0.01)。TSS组住院期间无一例发生急性排斥反应,NTSS组和TSS组28 d病死率分别为42%和60%,比较差异无统计学意义(P>0.05)。除NTS组IFN-γ水平与健康人群比较差异无统计学意义外,其余脓毒症患者外周血TNF–α、IL-10和HMGB1 mRNA表达均显著高于健康人群(P均< 0.01)。TSS组和NTSS组TNF–α、IL-10和HMGB1mRNA表达水平均分别高于TS组和NTS组(P均< 0.01),TS组和TSS组TNF–α、IL-10分别高于NTS组和NTSS组(P< 0.05或0.01)。TSS组和NTSS组IFN-γ/ IL-4均较健康人群明显下降(P< 0.05或0.01)。结论免疫抑制剂的使用使肝移植患者合并脓毒症时病理生理改变更为复杂和严重,“个体化”的免疫调理治疗有助于重建机体免疫平衡。
Objective To investigate the change of inflammatory/anti-inflammatory cytokine in liver transplant patients at different stage of sepsis. Methods 47 patients complicated with sepsis in SICU of the Third Affiliated Hospital of Sun Yat-sen University from Jan 2009 to Dec 2010 were divided into 4 groups according to the type of surgery and the stage of sepsis: A. sepsis after transplantation (TS group, n=11), B. severe sepsis after transplantation (TSS group, n=10), C. sepsis without transplantation (NTS group, n=15) and D. severe sepsis without transplantation (NTSS group, n=11). 20 healthy volunteers were selected as control group. Blood samples were collected from patients to measure plasma TNF-α、IL-4、IL-10、IFN-γ and high mobility group box1(HMGB1)mRNA expression level. APACHEⅡ、SOFA score and mortality of 28 day were recorded. Immunosuppresant therapy was withdrawn from TSS group and patients were received immune modality therapy.Result APACH and SOFA score in TSS and NTSS group were significantly higher than those in TS and TSS group respectively(all P < 0.01). Moreover, SOFA score of TSS group was significantly higher than that of NTSS group(P < 0.01). There was no acute rejection occurred in TSS group. The mortality rates of NTSS group and TSS group were 42.2% and 60% respectively, and there was no significantly difference between these two groups(P>0.05). Except IFN-γ level of NTS group, TNF–α、IL-4、IL-10、IFN-γ and HMGB1mRNA expression in patients with sepsis were all higher than healthy person(P < 0.01). Comparison between groups showed that TNF–α、HMGB1mRNA expressionand IL-10 level in TSS group and NTSS group were higher than those in TS group and NTS group respectively(all P < 0.01). TNF–α and IL-10 in TS group and TSS group were higher than that in NTS group and NTSS group respectively(P < 0.05 or 0.01). IFN-γ/IL-4 in TSS group and NTSS group were significantly lower than that in healthy person (P < 0.05), and the decrease trend in TSS group was much obvious than that of NTSS group. Conclusion The pathophysiological change in liver transplant patients becomes more complicated and severe for the usage of immunosuppressant. Personal immune modality therapy helps to rebuild the balance of immunity.