POSTOPERATIVE ILEUS INDUCED BY SURGICAL TRAUMA

手术创伤引起的术后肠梗阻

• 批准号: 6180890
• 负责人: ANTHONY J BAUER
• 金额: $ 22.69万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6180890
• 关键词: cell migration; clinical research; cytokine; human tissue; intestine obstruction; intestines; laboratory rat; leukocyte adhesion molecules; macrophage; neuroregulation; nitric oxide; pathologic process; postoperative complications; prostaglandins; smooth muscle

DESCRIPTION: (Adapted from the applicant's abstract). Postoperative ileus, the surgically induced temporary impairment of coordinated propulsive intestinal peristalsis, remains a well-documented and almost universal consequence of human abdominal surgery. Despite its frequency and economic impact, accounting for prolonged hospital stays and patient discomfort, little is known for the underlying cellular mechanisms of this surgical conundrum. The investigators have demonstrated that there is, in the normal intestine, an extraordinarily dense and organized network of macrophages within the intestinal muscularis, which can be readily and promptly activated. In addition, they have shown that after macrophage activation, the jejunal circular muscle layer becomes massively infiltrated with numerous leukocyte populations, concurrently associated with a severe impairment in circular muscle function. Based on this data, they hypothesize that simple, mild surgical manipulation of the intestine initiates an inflammatory cascade within the circular smooth muscle layer, which results in the suppression of the intestinal neuromuscular apparatus and ileus. The PI and co-workers have designed a sequential series of experiments, pursuant to their preliminary data, suggesting that postoperative ileus is, at least in part, the end result of a series of molecular and inflammatory events set in motion within the circular smooth muscle of the gut following manipulation. Their preliminary data sketches out a scenario where surgical manipulation of the intestine results in gene induction and the activation of the dense resident muscularis macrophage network. These molecular events, then, lead to the secretion of kinetic substances (nitric oxide and prostaglandins) and the production of pro-inflammatory cytokines. The initial secretions of local macrophage- derived substances cause an initial phase of intestinal muscular dysfunction, which is of a relatively moderate degree and short duration. However, additionally the burst of macrophage cytokine genes causes the up-regulation of adhesion molecules, which then lead to leukocyte emigration and degranulation (nitric oxide, prostaglandins, oxygen radicals, and proteases). This extravasation and release of reactive substances subsequently induces a second phase of muscle and neural dysfunction with is associated with physical damage of a greater degree and duration. The process is most concentrated in the circular muscle; the investigators hypothesize that such a concentration is mechanistically due to the primary role of the endogenous tissue macrophages in this muscle layer.

描述：（改编自申请人的摘要）。术后肠梗阻， 手术引起的协调推进暂时性障碍 肠梗阻，仍然是一个有据可查，几乎普遍 人类腹部手术的后果。尽管它的频率和经济 影响，导致住院时间延长和患者不适， 对于这种外科手术的潜在细胞机制知之甚少， 难题调查人员已经证明，在 正常的肠道，一个非常密集和有组织的网络， 肠肌层内的巨噬细胞，这可以很容易地， 立即激活。此外，他们还表明， 激活，空肠环形肌层变得大量 大量白细胞浸润，同时伴有 循环肌功能严重受损根据这些数据， 他们假设简单温和的肠道手术 在环形平滑肌层内引发炎症级联反应， 导致肠道神经肌肉器官受到抑制 肠梗阻PI和同事们设计了一系列 实验，根据他们的初步数据，这表明， 术后肠梗阻至少部分是一系列肠梗阻的最终结果。 分子和炎症事件在圆形光滑的 在操作后的肠道肌肉。他们的初步数据草图 手术操作肠道会导致 基因诱导和致密驻留肌层的激活 巨噬细胞网络这些分子事件，然后，导致分泌 动力物质（一氧化氮和三尖杉酯碱）和生产 促炎细胞因子。局部巨噬细胞的初始分泌物- 衍生物质引起肠肌肉的初始阶段 功能障碍，这是一个相对中度和短期的。 然而，另外，巨噬细胞细胞因子基因的爆发导致了细胞凋亡。 粘附分子的上调，然后导致白细胞 迁出和脱粒（一氧化氮、胰高血糖素、氧 自由基和蛋白酶）。这种外渗和释放的反应性 物质随后诱导肌肉和神经的第二阶段， 功能障碍与更大程度的身体损伤有关 和持续时间。这个过程主要集中在环形肌肉中; 研究人员假设，这种浓度是机械地由于 内源性组织巨噬细胞在肌肉中的主要作用 层.