NUTRIENT ESSENTIAL FATTY ACIDS & GASTRIC MUCOSAL INJURY

我们建议研究营养必需脂肪酸的作用 (全民教育)-即花生四烯酸和亚油酸在预防和治疗糖尿病中的作用 乙醇、阿司匹林和乙醇对大鼠胃黏膜损伤的实验研究 牛磺胆酸。我们将确定：1)急性和/或慢性 服用EFA可a)预防或减轻胃粘膜损害或b) 加速既往损伤的愈合；2)全民教育饮食不足 易导致胃粘膜损伤，增加其程度或延缓 治疗，以及负责这些效果的机制(S)。其基本原理是 因为这些研究是全民教育是天然的饮食前体 前列腺素已被证明可以保护胃粘膜免受 急性损伤所产生的损伤性因素及加速愈合 人的胃十二指肠溃疡。研究将在雄性斯普拉格犬身上进行 接受以下治疗的Dawley大鼠：(1)单剂EFA作为预处理或作为 治疗后粘膜损伤，(2)EFA饮食不足10周， (3)富含EFA的饮食10周；(4)EFA充足的饮食(对照组)。 急性胃内注射会造成胃粘膜损伤 服用无水乙醇、酸化阿司匹林或牛磺胆酸。 胃粘膜损伤，其愈合和粘膜保护 评估：A)宏观上通过评分和计算机图像分析B) 组织学与形态计量学定量坏死C)通过 粘膜细胞增殖动力学的超微结构测定 具有扫描和透射式电子显微镜E)功能 测量离子通量、电位差和胃内pH，以及 F)通过测量DNA、蛋白质和血液的腔内损失来进行生化 以及胃内容物中前列腺素的浓度。至 探索全民健身促进胃粘膜保护的机制(S) 研究：(1)DNA和蛋白质合成抑制剂的作用 用于全民教育保护的微管和微丝干扰剂；(2) 修复的表面上皮对后续损伤的抵抗力；(3)作用 EFA对分离的胃粘膜细胞(表面、增殖区)的影响 它们的生存能力和产生前列腺素的能力。我们的长期计划 目标是评估营养全民教育的价值(和应用) 对人胃十二指肠粘膜损伤的预防和修复。

We propose to investigate the role of nutrient essential fatty acids (EFA)-namely arachidonic and linoleic in the prevention and healing of gastric mucosal injury in the rat produced by ethanol, aspirin and taurocholic acid. We will determine whether: 1) acute and/or chronic administration of EFA may a) prevent or reduce gastric mucosal damage or b) speed up healing of pre-existing injury; 2) diet deficient in EFA predisposes to gastric mucosal injury, increases its extent or delays healing, and the mechanism(s) responsible for these effects. The rationale for these studies is that EFA are natural DIETARY precursors of prostaglandins which have been shown to protect the gastric mucosa against acute injury produced by damaging factors and to accelerate healing of gastroduodenal ulcers in man. Studies will be performed on male Sprague Dawley rats receiving: (1) single dose of EFA as a pretreatment or as a posttreatment of mucosal injury, (2) diet deficient in EFA for 10 weeks, (3) diet rich in EFA for 10 weeks, (4) diet sufficient in EFA (controls). Gastric mucosal injury will be produced by acute intragastric administration of absolute ethanol, acidified aspirin or taurocholic acid. Gastric mucosal damage, its healing and mucosal protection will be assessed: A) macroscopically by scoring and computerized image analysis B) histologically with morphometric quantitation of necrosis C) by determination of mucosal cell proliferation kinetics D) ultrastructurally with scanning and transmission electromicroscopy E) functionally by measurements of ionic fluxes, potential difference and intragastric pH, and F) biochemically by measurements of luminal loss of DNA, protein and blood and the concentration or prostaglandins in the gastric contents. TO EXPLORE THE MECHANISM(S) OF EFA PROMOTED GASTRIC MUCOSAL PROTECTION WE PLAN TO STUDY: (1) THE EFFECT OF DNA AND PROTEIN SYNTHESIS INHIBITORS AND OF MICROTUBULES AND MICROFILAMENTS DISRUPTIVE AGENTS ON EFA PROTECTION; (2) RESISTANCE OF RESTORED SURFACE EPITHELIUM TO SUBSEQUENT INJURY; (3) ACTION OF EFA ON ISOLATED GASTRIC MUCOSAL CELLS (SURFACE, PROLIFERATIVE ZONE) THEIR VIABILITY AND ABILITY TO GENERATE PROSTAGLANDINS. Our long term objective is an assessment of the value (and application) of nutrient EFA in prevention and healing of gastroduodenal mucosal injury in man.