Analysis of pathophysiology of bacterial translocation under surgical stress.

细菌易位是导致败血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)或高细胞分裂素血症的关系尚未得到评估。在这项研究中，临床和实验研究评估了肠道完整性降低的病理生理学机制和潜在的治疗方法。1)在大的腹部手术(食道切除、胰腺切除、全胃切除)后不久，肝素后血浆二胺氧化酶(DAO)活性(PhD活性)下降，这是肠粘膜完整性的指标。PHD活性降低与血促炎性细胞因子、白介素6(IL-6)、SIRS水平升高呈负相关，提示二者之间存在相关性。2)在用Caco-2单层细胞(肠粘膜上皮模型)进行的体外研究中，在培养液中加入IL-6直接降低DAO活性并刺激…更多的大肠杆菌通过具有完整的核质结构的跨细胞途径通过细胞。结果提示，手术应激下肠道完整性降低和细菌易位是其直接机制。3)肠内喂养，辅以膳食纤维和支链氨基酸，与不加肠内营养相比，可促进术后PHD活性下降的恢复，从而有效地改善肠粘膜的完整性。4)对两种不同营养底物作为肠道喂养的营养底物进行了评价。说明了饮食核苷酸对维持小鼠血中中性粒细胞黏附分子(Mac-1、LFA-1)和氧化猝发功能的重要性。二十碳五烯酸是omega 3多不饱和脂肪酸之一，与omega 6或9多不饱和脂肪酸相比，利用Caco-2单层细胞改变了紧密连接的通透性。这些结果将为病理生理学和未来保持肠道完整性的免疫营养提供新的见解。较少

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