Fändriks L, von Bothmer C, Johansson B, Holm M, Bölin I, Pettersson A
Department of Surgery, Göteborg University, Sweden.
Gastroenterology. 1997 Nov;113(5):1570-5. doi: 10.1053/gast.1997.v113.pm9352859.
BACKGROUND & AIMS: The pathophysiology behind Helicobacter pylori-induced gastroduodenal dysfunction is incompletely understood. The aim of this study was to investigate if a water extract of H. pylori distorts acid-induced duodenal mucosal alkaline secretion.
Chloralose-anesthetized rats were prepared for duodenal luminal perfusion and in situ pH-stat titration of mucosal alkaline secretion.
Mucosal bicarbonate secretion increased approximately 55%-60% after a 5-minute exposure to 10 mmol/L HCl. This response was absent when water extracts of three strains of H. pylori (protein content, 0.2-20 microg/mL) had been added to the perfusate. Presence of 3 mmol/L L-arginine, but not the stereoisomer D-arginine, in the luminal perfusate reversed the H. pylori extract blockade of acid-induced mucosal alkaline secretion. High-performance liquid chromatography-based analyses showed that the endogenous nitric oxide synthase inhibitor asymmetric dimethyl arginine (ADMA) increased fourfold in duodenal perfusate and fivefold in duodenal tissue after H. pylori extract exposure. In vitro proteolysis of H. pylori extract also resulted in a substantial accumulation of ADMA. Exogenously administered ADMA, giving similar tissue concentrations, inhibited the mucosal alkaline response to acid exposure.
Water extracts of H. pylori inhibit acid-induced mucosal alkaline secretion via interference with mucosal NO synthase.
幽门螺杆菌诱导胃十二指肠功能障碍背后的病理生理学机制尚未完全明确。本研究旨在探究幽门螺杆菌水提取物是否会干扰酸诱导的十二指肠黏膜碱性分泌。
制备用氯醛糖麻醉的大鼠，用于十二指肠腔内灌注及黏膜碱性分泌的原位pH稳态滴定。
暴露于10 mmol/L盐酸5分钟后，黏膜碳酸氢盐分泌增加约55%-60%。当向灌注液中添加三株幽门螺杆菌的水提取物（蛋白质含量为0.2-20μg/mL）时，这种反应消失。管腔内灌注液中存在3 mmol/L L-精氨酸而非其立体异构体D-精氨酸，可逆转幽门螺杆菌提取物对酸诱导的黏膜碱性分泌的阻断作用。基于高效液相色谱的分析表明，暴露于幽门螺杆菌提取物后，十二指肠灌注液中的内源性一氧化氮合酶抑制剂不对称二甲基精氨酸（ADMA）增加了四倍，十二指肠组织中增加了五倍。幽门螺杆菌提取物的体外蛋白水解也导致ADMA大量积累。给予组织浓度相似的外源性ADMA可抑制黏膜对酸暴露的碱性反应。
幽门螺杆菌水提取物通过干扰黏膜一氧化氮合酶来抑制酸诱导的黏膜碱性分泌。
