Qiu B, Pothoulakis C, Castagliuolo I, Nikulasson Z, LaMont J T
Section of Gastroenterology, Boston University Medical Center Hospital, Massachusetts, USA.
Gastroenterology. 1996 Aug;111(2):409-18. doi: 10.1053/gast.1996.v111.pm8690206.
BACKGROUND & AIMS: Intestinal inflammation is associated with increased synthesis of nitric oxide, whereas inhibition of NO synthase (NOS) reduces experimental chronic intestinal inflammation. The aim of this study was to test the effects of NO blockers and donors on acute intestinal inflammation induced by Clostridium difficile toxin A in rat ileum.
Rats received NOS inhibitors or NO donors before measurement of toxin-mediated ileal secretion and permeability changes. Mucosal mast cell and neutrophil activity were measured by release of rat mast cell protease II and myeloperoxidase activity, respectively.
NOS inhibitors augmented but an NO donor inhibited toxin A-mediated ileal secretion and permeability when given before but not after toxin administration. Neither an NOS inhibitor nor an NO donor had any effect on cholera toxin-mediated secretion. Mast cell degranulation and neutrophil infiltration occurred after injection of toxin A or an NOS inhibitor, whereas the NO donor blocked both toxin A effects.
NOS inhibitors augmented and an NO donor blocked the intestinal effects of toxin A but not of cholera toxin. NO protects against toxin A by inhibition of intestinal mast cells and neutrophils, which are activated by toxin A, but not by cholera toxin.
肠道炎症与一氧化氮合成增加有关，而抑制一氧化氮合酶（NOS）可减轻实验性慢性肠道炎症。本研究旨在测试一氧化氮阻滞剂和供体对艰难梭菌毒素A诱导的大鼠回肠急性肠道炎症的影响。
在测量毒素介导的回肠分泌和通透性变化之前，给大鼠给予NOS抑制剂或一氧化氮供体。分别通过大鼠肥大细胞蛋白酶II的释放和髓过氧化物酶活性来测量黏膜肥大细胞和中性粒细胞活性。
在毒素给药前而非给药后给予NOS抑制剂可增强毒素A介导的回肠分泌和通透性，而一氧化氮供体则抑制该作用。NOS抑制剂和一氧化氮供体对霍乱毒素介导的分泌均无影响。注射毒素A或NOS抑制剂后会发生肥大细胞脱颗粒和中性粒细胞浸润，而一氧化氮供体可阻断毒素A的这两种作用。
NOS抑制剂增强而一氧化氮供体阻断毒素A对肠道的作用，但不影响霍乱毒素。一氧化氮通过抑制被毒素A激活的肠道肥大细胞和中性粒细胞来抵御毒素A，但不影响霍乱毒素。
