摘要
目的分析严重脓毒症患者的免疫炎症反应紊乱状态，探讨连续血液净化、α1，胸腺肽以及两者联用对免疫炎症反应紊乱及预后的影响。方法年龄〉18岁、Marshall评分〉5分的严重脓毒症患者91例，监测血清白细胞介素（IL）-6、IL-10、TNFα水平和单核细胞人白细胞DR抗原（HLA—DR）、T淋巴细胞计数的动态变化；并随机分为血液净化组、胸腺肽组、联合组和对照组。血液净化组连续3d应用连续性肾脏替代治疗（CRRT）或分子吸附再循环系统（MARS）治疗，同时给予经典SSC治疗；胸腺肽组皮下注射α1胸腺肽1．6mg／d，连续7d，同时给予经典SSC治疗；联合组：联合应用血液净化组和胸腺肽组治疗方案；对照组给予经典SSC治疗。观察患者治疗前及治疗后3、7d以上免疫炎症指标及临床预后。结果与健康对照组比较，严重脓毒症患者血清IL-6、IL-10、IL-6／IL-10和TNFec明显升高，HLA—DR、CD3^＋、CD4^＋和CD8^＋T淋巴细胞明显降低（P〈0．05或P〈0．01），与存活者比较，死亡患者血清IL-6、IL-6／IL-10、TNFα、HLA—DR、CD3^＋、CD4^＋和CD8^＋变化更明显（P〈0．05或P〈0．01）。与对照组同期比较，胸腺肽组治疗后7dCD3^＋明显升高（P〈0．05），血液净化组和联合组治疗后7d IL-6、IL-6／IL-10和TNFα均明显下降，HLA—DR、CD3、CD4和CD8均明显增高，且联合组治疗后3dTNFα已有明显下降，CD3^＋和CD4^＋就已明显升高（P〈0．05或P〈0．01）；与胸腺肽组同期比较，血液净化组和联合组所有指标均有改善，但仅联合组治疗后3dCD3^＋明显升高，治疗后7dIL-6／IL-10明显下降（P〈0．05）；3个治疗组28d内机械通气时间、ICU停留时间均有缩短，28d病死率和90d病死率均有下降，其中血液净化组ICU停留时间、联合组28d内机械通气时间和ICU停留时间明显缩短（P〈0．05）。结论严重脓毒症患者全身炎症反应和免疫抑制同时存在；α1胸腺肽具有免疫增强的作用，连续血液净化具有抗炎和免疫增强双向调节作用；两者均可改善患者临床预后，且联用后效果更好。
Objective To investigate the immune and inflammation confusion state in severe sepsis and the effects of two way immunomodulation therapy with continuous blood purification （CBP）, thymosin α1, and combined therapy of CBP and thymosin α1. Methods 91 Patients with severe sepsis aged 〉 18, with Marshall score 〉 5. were randomly divided into 4 groups： CBP Group （n = 22） undergoing continuous renal replacement therapy （CRRT） or molecular adsorbents recirculating system （ MARS ） therapy once a day for 3 days in addition to classical Surviving Sepisis Campaign （SSC） therapy, Thymosin α1 Group （n = 23 ） undergoing subcutaneous injection of tbymosin α1 1.6 mg once a day for 7 days in addition to SSC therapy, Combined Therapy Group （n = 22） undergoing CBP combined with thymosin α1 treatment in addition to SSC therapy, and SSC Group （ treatment control group, n = 24 ） undergoing SSC therapy only.Peripheral blood samples were collected before treatment, and 3 and 7 days after the beginning of treatment （ days 4 and 8） to detect the serum interleukin （IL） -6, IL-10, and tumor necrosis factor （TNF） -α The levels of CD14^＋ monocyte human leucocyte antigen （ HLA）-DR and T lymphocytes were monitored. The mechanical ventilation time, ICU stay length, and mortality within 28 d and mortality within 90 d were observed. Ten healthy persons were used as healthy control group. Results Thirty-four of the 91 patients died within 28 d with a mortality of 77.4% （ Death Group） and other 57 patients were put in Survival Group. The levels of serum IL-6, IL-10, and TNFα, and IL-6/IL-10 at different time points of both Death and Survival Groups were all significantly higher, and the HLA-DR level, and CD3^＋ , CD4^＋ , and CDs T lymphocyte numbers at different time points of both Death and Survival Groups were all significantly lower than those of the healthy controls （P 〈 0. 05 or 〈 0. 01 ）. The levels of serum IL-6, IL-6/IL-10, TNFα, HLA-DR, and CD3^＋, CD4^＋, and CDs T lymphocyte at different time points of Death Group were all significantly higher than those of Survival Group （P 〈0. 05 or 〈0. 01 ）. The CD3^＋ T lymphocyte number on day 8 of Thymosin Group was significantly higher than that of SSC Group （ all P 〈 0. 05）. The serum IL-6 and TNFα and IL-6/IL-10 were decreased, and HLA-DR, and CD3^＋, CD4^＋, and CDs were increased significantly on day 8 in CBP and Combined Therapy Groups. The level of TNFα decreased, and the numbers of CD3^＋ and CD4^＋ T lymphocytes increased significantly on day 4 in Combined Therapy Group（ P 〈 0. 05 or P 〈 0.01 ）. Compared with Thymosin Group, almost all the indexes of CBP and Combined Therapy Groups were improved, only the CD3^＋ T lymphocyte level on day 4 increased and the IL-6/IL-10 ratio on day 8 was decreased significantly in Combined Therapy Group （ both P 〈 0. 05 ）. Compared with those of SSC Group, the mechanical ventilation time, length of ICU stay within 28 days, and 28 days mortality and 90 days mortality of the 3 treatment groups were all decreased, and there were statistical differences in the length of ICU stay of CBP Group and in the mechanical ventilation time and length of ICU stay within 28 days of Combined Therapy Group （both P 〈 0. 05 ） . Conclusion Systemic inflammatory response and immunodepression exist simultaneously in severe sepsis. Thymosin α1 increases the cellular immunity, and CBP bi-modulates the immune turbulence, reduces the inflammatory mediators, and meliorates the immune homeostasis. These 2 therapies also improve the clinical prognosis and the combination of both would be more effective.
出处
《中华医学杂志》
CAS
CSCD
北大核心
2009年第15期1028-1033,共6页
National Medical Journal of China
基金
广东省科技计划基金（2004836001005）
佛山市重点科技攻关项目（04080081）
关键词
脓毒症
连续血液净化
胸腺肽
免疫
炎症
随机对照试验
Sepsis
Continuous blood purification
Thymosin
Immunity
Inflammation
Randomized controlled trials
