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口服给予小鼠的固醇合成抑制剂25-羟基胆固醇和7-酮胆固醇的作用。

Effects of 25-hydroxycholesterol and 7-ketocholesterol, inhibitors of sterol synthesis, administered orally to mice.

作者信息

Kandutsch A A, Heiniger H J, Chen H W

出版信息

Biochim Biophys Acta. 1977 Feb 23;486(2):260-72. doi: 10.1016/0005-2760(77)90022-4.

DOI:10.1016/0005-2760(77)90022-4
PMID:836857
Abstract

When 25-hydroxycholesterol or 7-ketocholesterol was fed to mice with the diet, growth was suppressed and mature mice lost weight. The effect of the 7-ketone upon body weight was effectively counteracted by cholesterol whereas cholestanol and beta-sitosterol were ineffective. Growth repression due to 25-hydroxycholesterol was only partially relieved by cholesterol. The effects of 25-hydroxycholesterol and 7-ketocholesterol upon body weight were related to an apparent effect upon appetite. However the sterols were not unpalatable since diets containing them were not rejected in favor of control diet. Intestinal sterol synthesis was inhibited soon after the administration of dietary 7-ketocholesterol or 25-hydroxycholesterol but inhibition decreased with prolonged feeding. When fed by gavage, the sterols suppressed intestinal sterol synthesis as soon as 2 h after administration. In contrast, cholesterol administered by gavage did not affect intestinal sterol synthesis during a 24 h test period. When fed with the diet 25-hydroxycholesterol and 7-ketocholesterol did not depress hepatic cholesterol synthesis beyond the low levels found in pair-fed controls. Inhibition of intestinal sterol synthesis was accompanied by a decrease in the concentration of cholesterol in the intestinal mucosa and, usually, by a drop in the molar ratio of cholesterol to phospholipids.

摘要

当将25-羟基胆固醇或7-酮胆固醇与食物一起喂给小鼠时,生长受到抑制,成年小鼠体重减轻。7-酮对体重的影响可被胆固醇有效抵消,而胆甾烷醇和β-谷甾醇则无效。25-羟基胆固醇导致的生长抑制仅部分被胆固醇缓解。25-羟基胆固醇和7-酮胆固醇对体重的影响与对食欲的明显作用有关。然而,这些固醇并非味道不佳,因为含有它们的食物并未被拒食而选择对照食物。在给予膳食7-酮胆固醇或25-羟基胆固醇后不久,肠道固醇合成即受到抑制,但随着喂养时间延长,抑制作用减弱。通过灌胃给予时,这些固醇在给药后2小时即抑制肠道固醇合成。相比之下,在24小时的测试期内,通过灌胃给予胆固醇对肠道固醇合成没有影响。当与食物一起喂养时,25-羟基胆固醇和7-酮胆固醇不会使肝脏胆固醇合成低于配对喂养对照组中发现的低水平。肠道固醇合成的抑制伴随着肠道黏膜中胆固醇浓度的降低,通常还伴随着胆固醇与磷脂摩尔比的下降。

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