POSTOPERATIVE ILEUS INDUCED BY SURGICAL TRAUMA

描述：(改编自申请人的摘要)。术后肠梗阻， 手术所致的暂时性协调推进功能障碍 肠蠕动，仍然是一种有充分证据且几乎普遍存在的 人类腹部手术的后果。尽管它的频率和经济 影响，包括住院时间延长和患者不适， 对这种外科手术的潜在细胞机制知之甚少。 难解之谜。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 肠道肌层内的巨噬细胞，它可以很容易地和 迅速启动。此外，他们还表明，巨噬细胞 激活时，空肠环状肌层变得巨大 渗透了大量的白细胞群，同时与 并有严重的环行肌功能障碍。根据这些数据， 他们假设，对肠道的简单、温和的外科操作 在环状平滑肌层内引发炎症级联反应， 这会导致肠道神经肌肉机构受到抑制 还有肠梗阻。PI和同事们设计了一系列连续的 根据他们的初步数据，实验表明 术后肠梗阻至少部分是一系列手术的最终结果。 分子和炎症事件在环形内平稳运动 推拿后的肠道肌肉。他们的初步数据草图 排除了这样一种情况，即手术操作肠道导致 基因诱导与致密驻留肌的激活 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)及其生产 促炎细胞因子。局部巨噬细胞的初始分泌物- 衍生物质导致肠道肌肉的初始阶段 功能障碍，程度相对适中，持续时间较短。 然而，此外，巨噬细胞细胞因子基因的突然爆发导致 上调黏附分子，进而导致白细胞 移民和脱颗粒(一氧化氮、前列腺素、氧气 自由基和蛋白酶)。这种反应性的渗出和释放 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害有关 和持续时间。这一过程最集中在环状肌； 调查人员假设，这种集中是机械性的。 内源性组织巨噬细胞在该肌肉中的主要作用 一层。

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.