乌司他丁联合胸腺肽α_1改善脓毒症患者免疫功能的作用机制研究

Effect of ulinastatin plus thymosin-α_1 therapy on improving immune function in septic patients

目的:研究乌司他丁联合胸腺肽α1免疫调理治疗改善脓毒症免疫功能的可能作用机制。方法:前瞻性分析70例符合重脓毒症患者,随机分成经典治疗组和经典治疗联合免疫调理治疗组,经典治疗组接受常规治疗,经典治疗联合免疫调理组使用常规治疗联合乌司他丁和胸腺肽α1治疗,免疫调理疗程为7d,分别观察治疗前和治疗后1、3、7d临床和相关免疫学指标,并收集临床资料和预后情况。结果:脓毒症患者仍以细菌感染为主,极少发生单纯真菌感染。病原菌常见于痰和腹腔引流液。免疫调理炎症因子的分析,经典治疗联合免疫调理治疗组TNF-α低于经典治疗组(P<0.05);经典治疗联合免疫调理治疗组IL-10高于经典治疗组(P<0.05)。免疫调理体液免疫的分析,经典治疗联合免疫调理治疗组的IgG水平高于经典治疗组(P<0.05);经典治疗联合免疫调理治疗组的IgA、IgM、补体C3和补体C4水平与经典治疗组比较无显著差异(P>0.05)。免疫调理细胞免疫的分析,经典治疗联合免疫调理治疗组CD4+T淋巴细胞高于经典治疗组(P<0.05),经典治疗联合免疫调理治疗组的淋巴细胞计数及CD14+单核细胞HLA-DR水平在7d较经典治疗组显著升高,持续至治疗后28d(P<0.05);经典治疗联合免疫调理治疗组患者机械通气和使用升压药的时间较经典治疗组明显缩短(P<0.05);但经典治疗联合免疫调理治疗组患者的ICU住院天数和ICU费用没有显著增加(P>0.05)。住院期间,经典治疗组死亡20例,与经典治疗联合免疫调理治疗组死亡13例比较(P<0.05);随访观察,经典治疗联合免疫调理治疗组远期生存时间明显延长(P<0.05)。结论:对以细菌感染为主的脓毒症患者免疫调理可以明显降低促炎因子TNF-α水平,升高抗炎因子IL-10水平,轻度提高IgG水平,升高淋巴细胞、CD4+T淋巴细胞和CD14+单核细胞HLA-DR水平,从而改善脓毒症患者的免疫麻痹。免疫调理治疗可以缩短脓毒症患者ICU内机械通气和升压药使用的时间,而不增加ICU住院天数和ICU费用。

AEM ： To investigate the effect of ulinastatin plus thymosin - α1 therapy on improving immune function in septic patients. METHODS： 70 patients wero divided into two groups. One group was classical treatment group （CT） with regular therapy and another group was classical treatment plus immunotherapy group （CIT） with ulinastatin plus thymosin - α1 for a week. The immune index before and after treatment on day 0, 1, 3 and 7 was observed, including the clinical and survival data. RESULTS： The most common pathogen of sepsis was bacteria, and infection by fungi was in rare. The common locations of bacteria observed were sputum and abdominal drainage. The level of TNF -α was significant lower in CIT group than that in CT group （ P 〈 0. 05 ）. IL - 10 level was significantly higher in CIT group than that in CT group （P 〈 0. 05 ）. IgG level was significant lower in CIT group than that in CT group （ P 〈 0.05 ）. No significant difference in the levels of IgA, IgM, C3 and C4 between two groups was observed （ P 〉 0. 05 ）. CD4＋ T lymphocytes were significant higher in CIT group than those in CT group （P 〈 0. 05 ）. From day 7 to day 28, the lymphocytes and level of HLA - DR in CD14＋ monocytes were significant higher in CIT group than those in CT group （ P 〈 0. 05 ）. The time of mechanical ventilation and vasopressors used in CIT group was shorter than those in CT group （ P 〈 0.05 ）. But the length of stay and the cost in ICU showed no significant increase between these two groups （ P 〉0. 05 ）. During hospitalization, 20 patients died in the CT group and 13 patients died in CIT group （ P 〈 0.05 ）. The long - term survival time in CIT group was longer than that in CT group （ P 〈 0. 05 ）. CONCLUSION ： Immunotherapy in septic patients can decrease TNF -α level and increase IL - 10 level. Immunotherapy in septic patients can increase IgG level slightly, CD4 ＋ T lymphocyte, and HLA - DR in CD14＋ monocytes, which improve the immune paralysis in septic patients. Immunotherapy can shorten the time of mechanical ventilation and vasopressors used, but it doesn＇t increase the length of stay and the cost.