NUTRIENT ESSENTIAL FATTY ACIDS & GASTRIC MUCOSAL INJURY

营养必需脂肪酸

基本信息

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
项目类别：
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

项目摘要

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.

我们建议研究营养必需脂肪酸的作用 (EFA) - 即花生四烯酸和亚油酸在预防和治疗中的作用乙醇、阿司匹林等对大鼠胃粘膜的损伤牛磺胆酸。我们将确定是否：1) 急性和/或慢性施用 EFA 可以 a) 预防或减少胃粘膜损伤或 b) 加速已有损伤的愈合； 2）饮食中缺乏EFA 容易引起胃粘膜损伤，增加其程度或延迟治愈，以及造成这些影响的机制。理由对于这些研究来说，全民教育是天然膳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男性胃十二指肠溃疡。研究将对男性斯普拉格进行 Dawley 大鼠接受：（1）单剂量 EFA 作为预处理或作为粘膜损伤治疗后，(2) 饮食缺乏 EFA 10 周， (3) 富含 EFA 的饮食持续 10 周，(4) 富含 EFA 的饮食（对照）。急性胃内出血会造成胃粘膜损伤给予无水乙醇、酸化阿司匹林或牛磺胆酸。胃粘膜损伤、其愈合和粘膜保护将评估：A) 通过评分和计算机图像分析进行宏观评估 B) 组织学上用形态计量学定量坏死 C) 粘膜细胞增殖动力学的测定 D) 超微结构具有扫描和透射电子显微镜 E) 功能离子通量、电位差和胃内 pH 值的测量，以及 F) 通过测量 DNA、蛋白质和血液的管腔损失进行生化分析以及胃内容物中前列腺素的浓度。到探索我们计划的全民教育促进胃粘膜保护的机制研究：(1) DNA 和蛋白质合成抑制剂的作用以及微管和微丝对全民教育保护的破坏性因素； (2) 恢复的表面上皮对后续损伤的抵抗力； (3) 行动 EFA 对分离胃粘膜细胞（表面、增殖区）的影响它们的活力和产生前列腺素的能力。我们的长期目标是评估营养素全民教育的价值（和应用）预防和治愈人类胃十二指肠粘膜损伤。