Nitric oxide in the gut.
Nitric oxide in the gut.
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发表时间：
1995-02
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通讯作者：
Salzman Al
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作者：
Salzman Al
摘要 一氧化氮（NO.）在胃肠道的生理学及其对危重疾病的反应中发挥着核心作用。 NO 的潜在来源。肠道中的微生物包括：内在肠组织（肥大细胞、上皮细胞、平滑肌、神经丛）、驻留和/或浸润白细胞（中性粒细胞、单核细胞）、胃腔硝酸盐的还原以及共生厌氧菌的反硝化作用。一氧化氮合酶的大脑和内皮亚型在静息条件下表达，而诱导型的诱导需要炎症刺激。在静息条件下，粘膜灌注受NO调节。来源于肠系膜床的血管内皮。炎症期间，NO 过多。诱导型合酶的产生可能导致粘膜充血。蠕动和括约肌作用的协调是由 NO 的释放介导的，NO 是非肾上腺素能、非胆碱能肠神经系统的主要神经递质。肠蠕动的改变，例如肠梗阻，是由 NO 浓度过高引起的。在内毒素中毒和炎症性肠病期间产生。 NO的作用。人们对盐和水分泌的调节知之甚少。内毒素诱导的胃酸分泌抑制似乎是由 NO 的作用介导的。壁细胞上。不。可以通过维持粘膜灌注、抑制中性粒细胞与肠系膜内皮的粘附、阻断血小板粘附和防止肥大细胞活化来保护胃肠粘膜免受各种刺激（腐蚀性摄入、缺血、缺血/再灌注损伤、早期内毒素休克）。但过量的NO.可能会直接损伤粘膜。 NO保护肠粘膜的屏障功能。在损伤的早期阶段，中性粒细胞粘附、缺血和肥大细胞激活相关。抑制NO。在炎症的更晚期阶段，当诱导型 NOS 的激活产生有毒浓度的 NO 时，合成可改善屏障功能障碍。在高浓度时，NO。破坏肌动蛋白细胞骨架，抑制 ATP 形成，扩张细胞紧密连接，并产生高渗透状态。选择性抑制 NOS 的诱导型亚型并维持其组成型可能具有治疗作用。
Abstract Nitric oxide (NO.) plays a central role in the physiology of the gastrointestinal tract and its response to critical illness. Potential sources of NO. in the gut include: intrinsic intestinal tissue (mast cells, epithelium, smooth muscle, neural plexus), resident and/or infiltrating leukocytes (neutrophils, monocytes), reduction of luminal gastric nitrate, and denitrification by commensal anaerobes. The brain and endothelial isoforms of nitric oxide synthase are expressed under resting conditions, whereas inflammatory stimuli are required for the induction of the inducible type. Under resting conditions, mucosal perfusion is regulated by NO. derived from the vascular endothelium of the mesenteric bed. During inflammation, excessive NO. production from the inducible synthase may contribute to mucosal hyperemia. Coordination of peristalsis and sphincteric action is mediated by the release of NO., which acts as the principal neurotransmitter of the nonadrenergic, noncholinergic enteric nervous system. Alterations in bowel motility, such as ileus, result from excessive concentrations of NO. generated during endotoxicosis and inflammatory bowel disease. The role of NO. in the regulation of salt and water secretion is poorly understood. Endotoxin-induced inhibition of gastric acid secretion appears to be mediated by the action of NO. on parietal cells. NO. may protect the gastrointestinal mucosa from a variety of stimuli (caustic ingestion, ischemia, ischemia/reperfusion injury, early endotoxic shock) by maintaining mucosal perfusion, inhibiting neutrophil adhesion to mesenteric endothelium, blocking platelet adhesion, and preventing mast cell activation. Excessive NO., however, may directly injure the mucosa. Barrier function of the intestinal mucosa is protected by NO. in the early stages of injury, when neutrophil adhesion, ischemia, and mast cell activation are relevant. Inhibition of NO. synthesis ameliorates barrier dysfunction during more advanced stages of inflammation, when activation of inducible NOS yields toxic concentrations of NO.. At high concentrations, NO. disrupts the actin cytoskeleton, inhibits ATP formation, dilates cellular tight junctions, and produces a hyperpermeable state. Selective inhibition of the inducible isoform of NOS and maintenance of the constitutive types may be therapeutic.