Systemic phosphatidylcholine pretreatment protects canine esophageal mucosa during acute experimental biliary reflux

AIM： To characterize the consequences of short-term exposure to luminal bile on mucosal mast cell reactions in a canine model, and to determine the effects of systemic phosphatidylcholine pretreatment in this condition. METHODS： Twenty mongrel dogs were used for experiments. Group 1 （n =5） served as a salinetreated control, while in group 2 （n = 5） the esophagus was exposed to bile for 3 h. In group 3 （n =5） the animals were pretreated with 7-nitroindazole to inhibit the neuronal isoform of nitric oxide synthase. In group 4 （n = 5） phosphatidylcholine solution （50 rng/kg） was administered iv before the biliary challenge. Mucosal microcirculation was observed by intravital videomicroscopy. Myeloperoxidase and nitric oxide synthase activities, the degrees of mast cell degranulation and mucosal damage were evaluated via tissue biopsies. RESULTS： Exposure to bile evoked significant mast cell degranulation and leukocyte accumulation. The red blood cell velocity and the diameter of the postcapillary venules increased significantly. The tissue ATP content and constitutive nitric oxide synthase activity decreased, while the inducible nitric oxide synthase activity increased significantly as compared to the control values. 7-nitroindazole treatment significantly exacerbated the mucosal mast cell degranulation and tissue damage. Tn contrast, phosphatidylcholine pretreatment prevented the bile-induced ATP depletion, the inducible nitric oxide synthase and myeloperoxidase activity and the mast cell degranulation increased. CONCLUSION： The neuronal nitric oxide synthasemast cell axis plays an important role in the esophageal mucosal defense system. Systemic phosphatidylcholine pretreatment affords effective protection through ameliorating the bile-induced ATP depletion and secondary inflammatory reaction.

瞄准：在一个犬的模型在粘膜桅杆房间反应上描绘短期的暴露的后果到钠胆汁，并且处于这个条件决定全身的 phosphatidylcholine 预告的处理的效果。方法：二十条杂种狗被用于实验。组 1 (n = 5 ) 用作盐对待的控制，当时在组 2 (n = 5 ) 食管为 3 h 暴露于胆汁。在组 3 (n = 5 ) 动物是有 7-nitroindazole 的 pretreated 禁止氮的氧化物 synthase 的神经元对碘氧基苯甲醚。在组 4 (n = 5 ) phosphatidylcholine 答案(50 mg/kg ) 被管理在胆汁的挑战前的 iv。粘膜的微循环被生活期内录像显微镜学观察。Myeloperoxidase 和氮的氧化物 synthase 活动，桅杆房间去粒的度和粘膜损坏经由织物活体检视被评估。结果：到胆汁的暴露唤起了重要桅杆房间去粒和白血球累积。红血房间速度和毛状的小静脉显著地增加了的柱子的直径。织物 ATP 内容和组成的氮的氧化物 synthase 活动减少了，当可诱导的氮的氧化物 synthase 活动作为与控制价值相比显著地增加了时。7-nitroindazole 处理显著地加重了粘膜桅杆房间去粒和织物损坏。相反， phosphatidylcholine 预告的处理阻止了导致胆汁的 ATP 弄空，可诱导的氮的氧化物 synthase 和 myeloperoxidase 活动，桅杆房间去粒增加了。结论：神经元的氮的氧化物 synthase -- 桅杆细胞轴在食道的粘膜防卫系统起一个重要作用。全身的 phosphatidylcholine 预告的处理通过改善负担得起有效保护导致胆汁的 ATP 弄空和第二等的炎性反应。