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豚鼠高脂血症与肝细胞色素P-450之间的关联。

Association between hyperlipidemia and hepatic cytochrome P-450 in guinea pigs.

作者信息

Roomi M W

机构信息

Linus Pauling Institute of Science and Medicine, Palo Alto, CA, USA.

出版信息

Res Commun Mol Pathol Pharmacol. 1997 Aug;97(2):139-50.

PMID:9344227
Abstract

The effects of ascorbic acid (AA) or vitamin C in atherosclerosis has attracted considerable attention; however results of clinical studies are conflicting. Several studies indicate an increase in plasma triglyceride (TG) and cholesterol (CH) levels in guinea pigs (GP) that have been fed a diet containing a minimal amount of AA. Previous studies carried out in GP fed a diet devoid of AA showed a significant decrease in cytochrome P-450 level compared to GP fed high and adequate amounts; however, the level of cytochrome P-450 in the two groups were not significantly different. The enzymes that synthesize TG and CH are located in endoplasmic reticulum which is also the site for cytochrome P-450 synthesis. It is of interest to determine whether there is an association between TG and CH synthesis and cytochrome P-450 induction. Adult male Hartley GP weighing 350-400 g were fed a diet containing 2.5% (Group I), 0.1% (Group II) and 0% (Group III) AA. The food consumption and weight gain were not significantly different in different groups. After feeding the diet for four weeks, half of the animals in each group were starved. Blood was withdrawn and TG and CH were determined in the serum. TG and CH were markedly elevated in both starved and nonstarved Group III GP; however, these levels were not altered in Group 1 and Group II GP. Plasma AA showed significant differences in all three nonstarved and starved groups. Plasma alpha-lipoprotein was decreased and beta-lipoprotein was increased in Group III GP. Hepatic CH and TG were also significantly elevated in Group III GP, and Groups I and II showed no changes. TG and CH showed a negative correlation with cytochrome P-450, whereas CH and TG showed a positive correlation. We conclude that AA deficiency causes extensive hyperlipidemia, feeding high level of AA does not alter the lipid metabolism and induction ofcytochrome P-450 is inversely related to TG and CH synthesis.

摘要

抗坏血酸(AA)或维生素C在动脉粥样硬化中的作用已引起相当大的关注;然而,临床研究结果相互矛盾。几项研究表明,喂食含极少量AA饮食的豚鼠(GP)血浆甘油三酯(TG)和胆固醇(CH)水平会升高。先前对喂食不含AA饮食的GP进行的研究表明,与喂食高含量和适量AA的GP相比,细胞色素P-450水平显著降低;然而,两组中的细胞色素P-450水平并无显著差异。合成TG和CH的酶位于内质网中,内质网也是细胞色素P-450合成的场所。确定TG和CH合成与细胞色素P-450诱导之间是否存在关联很有意义。给体重350 - 400克的成年雄性Hartley GP喂食含2.5%(第一组)、0.1%(第二组)和0%(第三组)AA的饮食。不同组的食物消耗量和体重增加没有显著差异。喂食四周后,每组一半的动物被禁食。采集血液并测定血清中的TG和CH。第三组禁食和未禁食的GP中TG和CH均显著升高;然而,第一组和第二组GP中的这些水平没有改变。所有三个未禁食和禁食组的血浆AA均有显著差异。第三组GP的血浆α-脂蛋白降低,β-脂蛋白升高。第三组GP的肝脏CH和TG也显著升高,而第一组和第二组没有变化。TG和CH与细胞色素P-450呈负相关,而CH和TG呈正相关。我们得出结论,AA缺乏会导致广泛的高脂血症,喂食高水平的AA不会改变脂质代谢,并且细胞色素P-450的诱导与TG和CH合成呈负相关。

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