Analysis of pathophysiology of bacterial translocation under surgical stress.

细菌易位是引起脓毒症或多器官衰竭的主要原因。然而，腹部手术后肠粘膜完整性与全身炎症反应综合征（SIRS）或高细胞因子血症之间的关系尚未得到评估。在本研究中，在临床和实验研究中评估了肠道完整性下降的病理生理学和潜在的治疗方式。1)肝素后血浆二胺氧化酶（DAO）活性（PHD活性）是衡量肠粘膜完整性的指标，在腹部大手术（食管切除术、胰腺切除术、全胃切除术）后不久降低。ph活性降低与血液促炎细胞因子、白细胞介素6 （IL-6）、SIRS水平升高呈负相关，提示两者之间存在相关性。2)在体外对肠粘膜上皮模型Caco-2单层细胞的研究中，在培养基中添加IL-6可直接降低DAO活性，刺激大肠杆菌在细胞核和细胞质结构完整的情况下通过跨细胞途径通过细胞。结果提示手术应激下肠道完整性下降和细菌易位的直接机制。3)与不添加EN相比，添加膳食纤维和支链氨基酸的肠内喂养有助于恢复术后下降的PHD活性，表明改善肠黏膜完整性的有效性。4)作为肠内喂养的营养底物，对两种不同的营养底物进行了评价。结果表明，膳食核苷酸对维持黏附分子（Mac-1、LFA-1）和氧化破裂对小鼠血中性粒细胞功能的影响。与欧米伽6或欧米伽9多不饱和脂肪酸相比，欧米伽3多不饱和脂肪酸之一二十碳五烯酸对Caco-2单层细胞紧密连接通透性的改变。这些结果将为保持肠道完整性的病理生理学和未来的免疫营养提供新的见解。少

Bacterial translocation is a major concern as a cause developing sepsis or multiple organ failure. However the relationship between intestinal mucosal integrity and systemic inflammatory response syndrome (SIRS) or hypercytokinemia has not been evaluated after abdominal surgery. In this study, pathophysiology of decreased intestinal integrity and potential therapeutic modality was evaluated in clinical and experimental studies.1)Postheparin plasma diamine oxidase (DAO) activity (PHD activity), indicator of intestinal mucosal integrity, decreased in patients shortly after major abdominal surgery (esophagectomy, pancreatectomy, total gastrectomy). Negative correlation between decreased PHD activity and elevated blood pro-inflammatory cytokine, interleukin 6 (IL-6), level or SIRS suggested the relationship between them. 2)In an in vitro study using Caco-2 monolayer cells, a model of intestinal mucosal epithelium, addition of IL-6 in the medium directly decreased DAO activity and stimulate … More d E. coli passage across cells by transcellular route with intact nuclear and cytoplasmic structure. The results suggest the direct mechanism of decreased intestinal integrity under surgical stress and to develop bacterial translocation. 3)Enteral feeding, supplemented with dietary fiber and branched chain amino acids, in comparison without EN facilitated recovery of decreased PHD activity after surgery indicating the effectiveness to improve intestinal mucosal integrity. 4)As a nutritional substrate of enteral feeding, two different nutritional substrate were evaluated. The importance of dietary nucleotide to keep adhesional molecule (Mac-1, LFA-1) and oxidative burst in blood neutrophil function in mice was shown. Eicosapentaenoic acid, one of omega 3 polyunsatureted fatty acid, changed on tight junction permeability using Caco-2 monolayer cells in comparison with omega 6 or 9 polyunsaturated fatty acid. These results would provide new insights of pathophysiology and future immunonutrition to keep intestinal integrity. Less