NUTRIENT ESSENTIAL FATTY ACIDS & GASTRIC MUCOSAL INJURY

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 乙醇、阿司匹林、 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） 加速原有损伤愈合; 2）缺乏EFA的饮食 易导致胃粘膜损伤，增加其程度或延迟 愈合，以及负责这些影响的机制。 的理由 EFA是天然的饮食前体， 已经显示出保护胃粘膜免受 急性损伤产生的损害因素和加速愈合 研究将在雄性Sprague大鼠中进行 道利大鼠接受：（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)（4）EFA充足组（对照组）。 急性胃内灌胃可引起胃粘膜损伤 给予无水乙醇、酸化阿司匹林或牛磺胆酸。 胃粘膜损伤后，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肉眼观察B） 组织学上坏死的形态定量C）， 粘膜细胞增殖动力学的测定D）超微结构 用扫描和透射电子显微镜E）功能上， 测量离子通量、电位差和胃内pH值，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 以及胃内容物中的甘草素浓度。 到 探讨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 微管和微丝破坏剂对EFA的保护作用（2） 恢复的表面上皮对随后损伤的抵抗力;（3）作用 EFA对分离的胃粘膜细胞（表面，增殖区）的影响 它们产生前列腺素的活力和能力。 我们的长期 目标是评估营养素全民教育的价值（和应用 对胃十二指肠粘膜损伤预防和修复作用。

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.