POSTOPERATIVE ILEUS INDUCED BY SURGICAL TRAUMA

手术创伤引起的术后肠梗阻

• 批准号: 6384317
• 负责人: ANTHONY J BAUER
• 金额: $ 23.08万
• 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/6384317
• 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力暂时受损 肠道蠕动，仍然是一个有据可查且几乎普遍存在的 人类腹部手术的结果。尽管其频率和经济性 影响，考虑到住院时间延长和患者不适， 对于这种手术的潜在细胞机制知之甚少 难题。调查人员已经证明，在 正常的肠道是一个异常致密且有组织的网络 肠肌层内的巨噬细胞很容易被 及时激活。此外，他们还表明，巨噬细胞后 激活后，空肠环形肌层变得大量 被大量白细胞群浸润，同时相关 循环肌功能严重受损。根据该数据， 他们假设对肠道进行简单、温和的手术操作 在圆形平滑肌层内引发炎症级联反应， 这会导致肠道神经肌肉器官受到抑制 和肠梗阻。 PI 和同事设计了一系列连续的 实验根据他们的初步数据表明 术后肠梗阻至少部分是一系列因素的最终结果 分子和炎症事件在圆形光滑组织内启动 操作后肠道肌肉。他们的初步数据草图 提出这样一种情况：对肠道进行手术操作会导致 基因诱导和致密驻留肌层的激活 巨噬细胞网络。然后，这些分子事件导致分泌 动力学物质（一氧化氮和前列腺素）和产生 促炎细胞因子。局部巨噬细胞的初始分泌物 衍生物质引起肠肌的初始阶段 功能障碍程度相对中等，持续时间较短。 然而，巨噬细胞细胞因子基因的爆发还导致 粘附分子上调，从而导致白细胞 迁移和脱颗粒（一氧化氮、前列腺素、氧气 自由基和蛋白酶）。这种反应性的外渗和释放 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。该过程最集中在环形肌中；这 研究人员假设这种浓度是由于机械原因造成的 内源性组织巨噬细胞在该肌肉中的主要作用 层。