OXIDIZING CHOLESTEROL ON GASTROINTESTINAL, METABOLISM & ENDOTHELIAL CELLS

关于氧化固醇的吸收或代谢知之甚少。 我们 比较了标记胆固醇和标记氧化固醇 （7-羟基胆固醇、7-羟基胆固醇和7-酮基胆固醇） 由4- 14 C-胆固醇、[26，26，26，27，27--2-H6]胆固醇、 和[23，24，25，26，27 - 13 C5]胆固醇。 胃肠道吸收 大鼠中的氧化固醇为91.5（0.3%），而胆固醇为75（1.1% （p<0.001）。 当静脉注射并随后进行GC/质谱分析时 在紫外分光光度法中，7（-羟基胆固醇以23倍的速率清除 胆固醇。 5分钟后，仅1.2（0.2%）的7（-羟基胆固醇 血浆中胆固醇残留量为28.0（1.7%）， 同时注射的甘油三酯乳剂保留。 静脉注射14 C-7 β-羟基胆固醇也能迅速地 从血浆中清除，广泛分布于组织中， 新陈代谢。 放射性标记的放射性核素的摄取率 培养的内皮细胞氧化固醇的含量是胆固醇的15.7倍 外排率是对照组的3.4倍， 胆固醇（p<0.001）。 氧化固醇穿过内皮细胞 单层细胞比胆固醇快4.3倍（p<0.001）。 分数 氧固醇通过内皮细胞层的转运增加62。 氧化固醇在代谢过程中被代谢为极性更强的代谢物。 内皮细胞转运 这些氧固醇性质提供了 增强胆固醇通过组织转运的机制， 防止氧化胆固醇的积累。

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.