严重腹腔感染患者免疫失衡与肠屏障功能障碍的关系

目的 研究严重腹腔感染患者外周血调节性T细胞(Treg)水平变化及与肠通透性改变的关系.方法 根据46例严重腹腔感染患者入院1 d的急性生理学与慢性健康状况评分系统Ⅱ(APACHEⅡ)评分分为轻型(8～10 分,13例);中型(11～15分,17例);重型(16～20分,10例);极重型(≥21分,6例)4组.按治疗指南采用统一综合疗法,观察入院1、3、7 d的APACHEⅡ评分,外周血内毒素(ET)、人白细胞DR抗原(HLA-DR)、Treg及尿乳果糖/甘露醇(L/M)比值,并统计患者住外科重症监护病房(SICU)的天数及28 d病死率.结果 46例患者平均住SICU(11.06±5.40)d;28 d病死率为13.04%,重型、极重型患者28 d病死率较轻、中型显著增加(P均<0.05).轻型、中型患者尿L/M比值及ET在7 d内显著下降(P<0.05或P<0.01),而重型以上患者则先有下降,7 d又升高.轻型、中型患者HLA-DR表达呈升高趋势;重型以上患者HLA-DR抗原表达则减少,Treg水平增高(P<0.05或P<0.01),且1、3、7 d L/M比值与Treg呈显著正相关相关系数(r)分别为0.749,0.870,0.910,P均<0.01].结论 严重腹腔感染时出现肠道屏障功能障碍及其引发的肠源性内毒素血症加重全身炎症反应并引发严重免疫失衡,7 d内轻型患者肠道及免疫功能有所恢复,但中型患者已出现下降趋势,重型患者肠道及免疫功能出现明显障碍并不断加重,而极重型患者肠道及免疫功能始终处于严重抑制状态,感染难以控制,同时导致肠道以外的其他器官功能损害,形成并加重MODS.

The relationship between immune imbalance and intestinal barrier dysfunction in patients with severe intra-abdominal infections

Objective To investigate the relationship between the change in regulatory T lymphocyte (Treg) in the peripheral blood and intestinal barrier dysfunction in the patients who suffered multiple organ dysfuction syndrome (MODS) induced by severe intra-abdominal infections. Methods Forty-six patients with severe intra-abdominal infections were enrolled in this study, and they were divided into four groups according to their first day acute physiology and chronic health evaluationⅡ (APACHEⅡ) scores: mild group (8-10, 13 cases), medium group (11-15, 17 cases), severe group (16-20, 10 cases) and extremely severe group (≥21, 6 cases). The therapeutic strategy was the same in all groups based on the "guideline of the severe sepsis and septic shock". The levels of endotoxin (ET), human leucocyte antigen-DR (HLA-DR) and the CD4+CD25+Treg in the peripheral blood, and lactulose/mannitol (L/M) ratio in the urine were determined on 1st, 3rd and 7th day after treatment. Finally, the mortality rate at 28 days and the length of stay in surgical intensive care unit (SICU) were recorded. Results In 46 patients, the average length of stay in SICU were (11.06±5.40) days, and the mortality rate at 28 days was 13.04%. But the mortality of the patients in severe and extremely severe groups was higher than other groups (all P<0.05). The levels of L/M ratio and ET began to lower in 7 days in mild group and medium group (all P<0.05), and in severe and extremely severe groups, these two indexes were decreased at first, but increased on 7th day. Moreover, the HLA-DR of mild and medium groups showed a tendency of elevation, but monocytic HLA-DR expression was depressed and circulating Treg markedly elevated in the critically ill patients (all P<0.05). There was a significant positive correlation between Treg and L/M ratio on 1, 3, 7 days correlation coefficients (r)=0.749, 0.870, 0.910, respectively, all P<0.01]. Conclusion An increase in intestinal permeability and a greater degree of immunosuppression are observed during severe intra-abdominal infections. This change becomes more severe coinciding with the degree of seriousness of the patients. This condition is improved in mild and medium grade patients in 7 days, but no improvement is found in severe patients, and it gets worse in the extremely severe patients in 7 days. These data support the concept that severe immunological imbalance occurred in the patients with severe intra-abdominal infections, and it is associated with intestinal barrier dysfunction and endotoxemia.