NUTRIENT ESSENTIAL FATTY ACIDS & GASTRIC MUCOSAL INJURY

营养必需脂肪酸

• 批准号: 3152634
• 负责人: ANDRZEJ S TARNAWSKI
• 金额: $ 9.63万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152634
• 关键词: acid base balance; arachidonate; artificial intelligence; aspirin; autoradiography; duodenal ulcer; electron microscopy; essential fatty acids; ethanol; gastric mucosa; gastrointestinal epithelium; gastrointestinal pharmacology; linoleate; membrane structure; nutrition related tag; pathogenic diet; prostaglandin inhibitors; prostaglandins; radiotracer; scanning electron microscopy; surfactant; tissue /cell culture; wound healing; acid base balance; arachidonate; artificial intelligence; aspirin; autoradiography; duodenal ulcer; electron microscopy; essential fatty acids; ethanol; gastric mucosa; gastrointestinal epithelium; gastrointestinal pharmacology; linoleate; membrane structure; nutrition related tag; pathogenic diet; prostaglandin inhibitors; prostaglandins; radiotracer; scanning electron microscopy; surfactant; tissue /cell culture; wound healing

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.

我们建议研究养分必需脂肪酸的作用 （EFA） - 预防和康复中的蛛网膜和亚油果 乙醇，阿司匹林和 牛胆酸。 我们将确定是否：1）急性和/或慢性 EFA的给药可以a）预防或减少胃粘膜损害或b） 加快预先存在的伤害的愈合； 2）饮食不足EFA 容易发生胃粘膜损伤，增加其范围或延迟 治愈以及负责这些影响的机制。 理由 对于这些研究是，EFA是自然的饮食前体 前列腺素已被证明可以保护胃粘膜免受 破坏因素造成的急性损伤并加速愈合 人类的胃du溃疡溃疡。 研究将在男性Sprague上进行 Dawley大鼠接受：（1）单剂量的EFA作为预处理或 粘膜损伤后治疗，（2）EFA饮食不足10周， （3）富含EFA的饮食持续10周，（4）饮食在EFA中足够（对照组）。 胃粘膜损伤将由急性胃内产生 绝对乙醇，酸化的阿司匹林或牛胆酸的给药。 胃粘膜损伤，其愈合和粘膜保护将是 评估：a）通过评分和计算机图像分析在宏观上b） 在组织学上与坏死的形态计量计量c） 粘膜细胞增殖动力学的测定d）超微结构 通过扫描和传输电显微镜e）在功能上通过 离子通量，电势差和胃内pH的测量值以及 f）通过测量DNA，蛋白质和血液的腔内损失的生化 以及胃含量中的浓度或前列腺素。 到 探索我们计划的EFA促进胃粘膜保护的机制 研究：（1）DNA和蛋白质合成抑制剂和 微管和微丝的破坏性剂在EFA保护方面； （2） 对恢复的表面上皮的抗性对随后的损伤； （3）行动 在分离的胃粘膜细胞上的EFA（表面，增殖区） 它们的生存能力和产生前列腺素的能力。 我们的长期 目标是对养分EFA的价值（和应用）的评估 在预防和愈合人胃粘膜损伤中。