DUODENAL MUCOSAL BICARBONATE SECRETION IN MAN

在美国，十二指肠溃疡仍然是一种常见疾病，与 严重的发病率、死亡率和超过3美元的经济成本 10亿/年。十二指肠溃疡的病理生理学研究已有报道。 针对“攻击性”因素，而“防御性”因素 保护人十二指肠免受酸消化性损伤尚未彻底 人十二指肠完全没有HCO3的分泌。最近进来的 体外和体内动物研究表明：十二指肠表面 上皮细胞静息时分泌HC03-，分泌显著增加 对激动剂(如H+、前列腺素E2和一些胃肠激素)的反应； 环氧合酶和碳酸酐酶抑制剂抑制十二指肠 HC03-分泌；十二指肠HCO3-分泌有梯度(近端 大于远端)；在动物体内，运输既涉及电子中和 (Cl-/HC03-交换)和电生机理。 这项建议的目的是：1)系统地检查活体 十二指肠黏膜碳酸氢盐分泌在无胆管和 胰腺碳酸氢盐-调节十二指肠HC03分泌的因素-和 它们的相对效力和效力将被确定，2)量化 正常人和十二指肠溃疡患者十二指肠HC03的分泌 (活动性和非活动性)和十二指肠炎，3)对比HC03分泌 近端和远端十二指肠节段确定十二指肠梯度 存在，4)确定调节十二指肠的机制 人的HC03-分泌物。 初步的人体活体研究表明：1)人类近端 可分离十二指肠无胰胆管分泌物和基底液 十二指肠近端HC03分泌量约为175umo1/cmcm·h，2) 腔内H+显著增加碳酸氢盐的分泌，3) C_1-与S04=显著减少的碳酸氢盐的实化 分泌表明存在C1-HC03-交换机制。 这些实验将提供关于 十二指肠HC03-分泌物的生理和病理生理学研究 十二指肠酸消化性疾病患者。这些结果将 可能对十二指肠溃疡的预防和治疗产生影响 相关疾病。

In the US duodenal ulcer remains a common disease associated with substantial morbidity, mortality, and economic cost of greater than $3 billion/yr. Studies of the pathophysiology of duodenal ulcer have been directed at the "aggressive" factors, while the "defensive" factors that protect the human duodenum from acid-peptic damage have not been thoroughly examined and HCO3-secretion by the human duodenum not at all. Recent in vitro and in vivo animal studies indicate that: the duodenal surface epithelial cells secrete HC03-at rest and secretion significantly increases in response to agonists (e.g. H+, prostaglandin E2, and some GI hormones); cyclooxygenase and carbonic anhydrase inhibitors suppress duodenal HC03-secretion; there is a gradient for duodenal HCO3- secretion (proximal greater than distal); and in animals transport involves both electroneutral (Cl-/HC03-exchange) and electrogenic mechanisms. The aims of this proposal are to: 1) Systematically examine in vivo duodenal mucosal bicarbonate secretion in segments free of biliary and pancreatic bicarbonate - factors that regulate duodenal HC03-secretion and their relative potencies and efficacies will be determined, 2) Quantitate duodenal HC03-secretion in normal subjects and patients with duodenal ulcer (active and inactive) and duodenitis, 3) Contrast HC03-secretion in proximal and distal duodenal segments to determine if a duodenal gradient exists, and 4) Determine the mechanisms that regulate duodenal HC03-secretion in man. Preliminary in vivo studies in man indicate: 1) The human proximal duodenum can be isolated free of pancreaticobiliary secretion and basal proximal duodenal HC03 secretion is approximately 175 umo1/cmcm-h, 2) Intraluminal H+ significantly increases bicarbonate secretion, and 3) Substantiation of C1- with S04= significantly decreased bicarbonate secretion indicating the presence of C1-HC03-exchange mechanism. These experiments will provide important information regarding the physiology and pathophysiolgy of duodenal HC03- secretion in health and patients with acid-peptic diseases of the duodenum. These results will likely have an impact on prevention and treatment of duodenal ulcer and related diseases.