OXIDIZING CHOLESTEROL ON GASTROINTESTINAL, METABOLISM & ENDOTHELIAL CELLS

氧化胆固醇对胃肠道、代谢的影响

• 批准号: 6118544
• 负责人: LOUIS H KRUT
• 金额: $ 0.4万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6118544
• 关键词: animal tissue; biomedical resource; intestines; lipids; spectrometry; technology /technique

Little is known about absorption or metabolism of oxysterols. We compared labeled cholesterol to labeled oxysterols (7(-hydroxycholesterol, 7(-hydroxycholesterol, and 7-ketocholesterol) prepared from 4-14C-cholesterol, [26,26,26,27,27,27--2-H6]cholesterol, and [23,24,25,26,27-13C5]cholesterol. Gastrointestinal absorption of oxysterols in rats was 91.5(0.3% compared to 75(1.1% for cholesterol (p<0.001). When injected intravenously and followed by GC/mass spectrometry, 7(-hydroxycholesterol was cleared at 23 times the rate of cholesterol. After 5 min only 1.2(0.2% of 7(-hydroxycholesterol remained in plasma whereas 28.0(1.7% of cholesterol and 40.0(2.5% of a triglyceride emulsion injected simultaneously remained. 14C-7(-hydroxycholesterol injected intravenously was also rapidly cleared from plasma, widely distributed in tissues, and extensively metabolized. The fractional rate of uptake of radio-labeled oxysterols by cultured endothelial cells was 15.7 times that of choles terol (p<0.001) and the fractional rate of efflux was 3.4 times that of cholesterol (p<0.001). Oxysterols traversed endothelial cell monolayers 4.3 times faster than cholesterol (p<0.001). Fractional oxysterol transport across endothelial cell layers was increased 62. Oxysterols were metabolized to more polar metabolites during endothelial cell transit. These oxysterol properties provide a mechanism for enhancing cholesterol transport through tissues and preventing accumulation of oxidized cholesterol.

对氧化甾醇的吸收或代谢知之甚少。我们 标记胆固醇与标记氧化甾醇的比较 (7(-羟基胆固醇、7(-羟基胆固醇和7-酮胆固醇)) 由4-14C-胆固醇，[26，26，26，27，27，27-2-H6]胆固醇， 和[23，24，25，26，27-13C5]胆固醇。胃肠吸收 大鼠体内的氧化甾醇含量为91.5(0.3%)，而胆固醇为75(1.1%) (宝洁0.001)。静脉注射，然后GC/MASS 光谱分析，7(-羟基胆固醇)的清除速度是 胆固醇的含量。5分钟后仅1.2(7(-羟基胆固醇)的0.2% 留在血浆中，而28.0(1.7%的胆固醇和40.0(2.5%的 同时注射的甘油三酯乳剂残留。 14C-7(-羟基胆固醇)静脉注射也迅速 从血浆中清除，在组织中广泛分布，并广泛 新陈代谢。放射性标记的摄取分数 培养内皮细胞产生的氧固醇是胆汁的15.7倍 Terol(p&lt；0.001)，外排分数是 胆固醇(P&lt；0.001)。氧固醇类药物对内皮细胞的作用 单分子膜比胆固醇快4.3倍(p&lt；0.001)。分数 氧固醇跨内皮细胞层的转运增加了62。 氧化甾醇在体内代谢成更多的极性代谢物。 内皮细胞转运。这些氧固醇属性提供了一种 增强胆固醇在组织和组织中的转运机制 防止氧化胆固醇的积聚。