Kakis G, Kuksis A
Can J Biochem Cell Biol. 1984 Jan;62(1):1-10. doi: 10.1139/o84-002.
Male Wistar rats were infused intravenously with various amounts (2-20 mL/24 h) of Intralipid or Intralipid containing cholesterol or plant sterols (5-100 mg/24h), and hepatic cholesterogenesis was monitored by measuring the incorporation of [1-14C]acetate into the nonsaponifiable sterols of liver slices. It was observed that the infusion of Intralipid alone resulted in a hypercholesterolemia that varied with the amount of Intralipid administered and that it was accompanied by up to a threefold increase in hepatic cholesterogenesis. Inclusion of cholesterol in the Intralipid at 5 mg/mL prevented the increase in hepatic cholesterol biosynthesis, while an inhibition of up to 95% of control synthesis was achieved when a total of 33 mg of cholesterol in 20 mL Intralipid was infused over a 24-h period. It is concluded that the feedback regulation of cholesterol biosynthesis is operative even when the entry of cholesterol bypasses the intestine and the lipoprotein synthesis taking place there and that Intralipid is a suitable medium for the intravenous introduction of a large mass of metabolically active cholesterol molecules. Similar infusions of mixed plant sterols failed to prevent the activation or inhibition of cholesterol biosynthesis, but the administration of much larger doses of plant sterols (100 mg) brought about a partial inhibition of hepatic cholesterogenesis. It is concluded that the presence of an alkyl group in the side chain prevents the plant sterols from an effective interaction with the critical sites of the feedback regulatory system of cholesterogenesis. The effects of the larger doses of plant sterols were attributed to the displacement of increasing amounts of free cholesterol from the vascular tissues, which resulted in an effective elevation of plasma cholesterol levels. The infusion of either cholesterol or plant sterols over the 24-h period did not appear to have a consistent effect upon the composition or secretion of biliary bile acids.
给雄性Wistar大鼠静脉注射不同剂量（2 - 20毫升/24小时）的脂质乳剂或含胆固醇或植物甾醇的脂质乳剂（5 - 100毫克/24小时），通过测量[1 - 14C]乙酸掺入肝切片非皂化甾醇中的量来监测肝脏胆固醇生成。观察到单独输注脂质乳剂会导致高胆固醇血症，其程度随脂质乳剂给药量的变化而变化，并且肝脏胆固醇生成最多可增加三倍。脂质乳剂中加入5毫克/毫升的胆固醇可防止肝脏胆固醇生物合成增加，而在24小时内输注20毫升含33毫克胆固醇的脂质乳剂时，可使对照合成抑制高达95%。得出的结论是，即使胆固醇的进入绕过肠道以及在肠道发生的脂蛋白合成，胆固醇生物合成的反馈调节仍然起作用，并且脂质乳剂是静脉内引入大量具有代谢活性的胆固醇分子的合适介质。类似的混合植物甾醇输注未能防止胆固醇生物合成的激活或抑制，但给予大得多剂量的植物甾醇（100毫克）会导致肝脏胆固醇生成部分受到抑制。得出的结论是，侧链中烷基的存在会阻止植物甾醇与胆固醇生成反馈调节系统的关键位点进行有效相互作用。较大剂量植物甾醇的作用归因于从血管组织中置换出越来越多的游离胆固醇，这导致血浆胆固醇水平有效升高。在24小时内输注胆固醇或植物甾醇似乎对胆汁酸的组成或分泌没有一致的影响。
