• 作者： 朱俊
• 作者服務機構： 美國德州萊斯大學生化系
• 中文摘要： 本藥劑（15-ketosterol）極具抑止膽固醇製造之功能。鼠類及猿猴類，經餵食此劑後，均產生可觀的降低血膽固醇之現象。本報告詳述15-ketosterol除抑止膽固醇製造外，更具有降低小腸吸收食物中膽固醇之功效。 在鼠類食物中，摻加此劑（0.05%），經十天餵食後，膽固醇吸收降低了62±18%。同時小腸吸收15-ketosterol之速率相當快，其吸收能力3-4倍高於膽固醇。 此劑之吸收路徑與膽固醇相似，經脂化過程後，其成為Chylomicrons之成分之一。使用靜脈注射此針劑，Chylo-microns很迅速地，有效地進入肝臟，脂化之15-ketosterol，在肝臟中還原為15-ketosterol。 同時發現15-ketosterol之生理代謝與膽固醇迥異。～85％之靜脈注射針劑，很快地排於膽汁中，而於同實驗中，只有～15％的膽固醇排出。 本篇報告之結論如下：此藥劑15-ketosterol（1）能有效抑止膽固醇製造，（2）能取代食物膽固醇之吸收，（3）並能迅速排於膽汁中。使得此劑將成為一種抗血管硬化症之有效藥劑。
• 英文摘要： 15-Ketosterol (5α-cholest-8(14)-en-3β-ol-15-one), a potent inhibitor for sterol synthesis, has shownhypocholesterolemic effects in rodents, baboons, and rhesus monkeys. In recent studies we demonstratedthat 15-ketosterol also exerted regulation on the input of cholesterol at the level of intestinal absorption.When Sprague Dawley rats were fed 0.05% 15-ketosterol in their chow for 10 days, a decrease in theabsorption of cholesterol into lymph by 62 ± 8% (n=4) was observed in the first 48 hrs after the intragasticinfusion of radiolabelled cholesterol. The absorption of cholesterol replaced by 15-ketosterol was furtherevidenced in the demonstration that the rats had a much more efficient rates of absorbing 15-ketosterol.Infusing rats with equal amount of the two sterols, the amount of 15-ketosterol absorbed was 3-4 foldthat of cholesterol in the initial 10 hrs. 15-Ketosterol was absorbed in and mainly esterified with 18:1 packed into intestinal chylomicrons.Upon the intravenous injection of chylomicrons isolated from other animals receiving 3H-15-ketosterolintragastrically, the rapid apparence of radioactivity in the liver suggested that chylomicrons were taken upeffectively. Ketosteryl ester was hydrolyzed back to 15-ketosterol in the liver. The metabolic fate of 15-ketosterol was very different from that of cholesterol. Over 85% of theadministered dose was recovered in the bile 38 hrs after intravenous injection of 15-ketosterol. In contrast,only 15% of cholesterol and/or its metabolites was slowly secreted in the bile. The replacement of dietary cholesterol absorption as well as the rapid and substantial secretion of15-ketosterol and its metabolites in the bile could significantly contribute to the hypocholesterolemicactivity of 15-ketosterol which could in turn reduce the risk of atherosclerosis.
• 中文關鍵字： oxysterol; hypocholesterolemic action; sterol absorption; bile secretion (Rats)
• 英文關鍵字： --