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大鼠静脉注射角鲨烯后的命运

Fate of intravenously administered squalene in the rat.

作者信息

Tilvis R S, Miettinen T A

出版信息

Biochim Biophys Acta. 1982 Aug 18;712(2):374-81. doi: 10.1016/0005-2760(82)90355-1.

DOI:10.1016/0005-2760(82)90355-1
PMID:7126611
Abstract

To investigate the metabolism of serum squalene rats were given intravenously serum or isolated lipoprotein containing [3H]squalene and [14C]cholesterol. Labeled squalene disappeared multiexponentially from serum and the rate of disappearance was consistently faster than for [14C]cholesterol. [3H]Squalene given by injection did not accumulate in tissues, but was rapidly cyclized to sterols, resulting in the labeling of serum methyl sterols and cholesterol as well as biliary and fecal sterols and bile acids. Independent of the form of administration, the fractional conversion of squalene to serum cholesterol was less than one. This was caused by the fact that [3H]squalene was eliminated initially more rapidly than serum [14C]cholesterol in the feces and was converted to a greater extent than serum cholesterol to bile acids, whereas both labels were eliminated in parallel as neutral sterols. The results support the role of newly synthesized hepatic cholesterol as the preferred substrate of bile acid synthesis.

摘要

为了研究血清角鲨烯的代谢,给大鼠静脉注射含有[3H]角鲨烯和[14C]胆固醇的血清或分离的脂蛋白。标记的角鲨烯从血清中呈多指数形式消失,其消失速率始终比[14C]胆固醇快。注射给予的[3H]角鲨烯不会在组织中蓄积,而是迅速环化为固醇,导致血清甲基固醇和胆固醇以及胆汁和粪便中的固醇和胆汁酸被标记。无论给药形式如何,角鲨烯向血清胆固醇的分数转化率均小于1。这是因为[3H]角鲨烯最初在粪便中的消除速度比血清[14C]胆固醇快,并且比血清胆固醇更多地转化为胆汁酸,而两种标记物作为中性固醇平行消除。这些结果支持新合成的肝脏胆固醇作为胆汁酸合成的首选底物的作用。

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A physiologically-based pharmacokinetic (PBPK) model of squalene-containing adjuvant in human vaccines.含角鲨烯佐剂的人类疫苗的基于生理学的药代动力学(PBPK)模型。
J Pharmacokinet Pharmacodyn. 2013 Oct;40(5):545-56. doi: 10.1007/s10928-013-9328-y. Epub 2013 Aug 4.
2
Sterol synthesis from biliary squalene in the jejunal mucosa of the rat in vivo.大鼠空肠黏膜中胆源性角鲨烯在体内合成固醇的过程。
Lipids. 1983 Aug;18(8):530-3. doi: 10.1007/BF02535392.