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苯丙酮尿症犬模型中难治阶段的发展

Development of a refractory stage in a dog model for phenylketonuria.

作者信息

Sharma S D, Cooley C, De La Pava E, Ambrus C M

出版信息

Res Commun Chem Pathol Pharmacol. 1981 Jul;33(1):145-53.

PMID:6455729
Abstract

Dogs were fed a continuous diet of phenylalanine (Phe) daily and para-chloro-phenylalanine (p-CPhe), an inhibitor of phenylalanine hydroxylase (PH-ase) every second day. It was reported that such a diet produces a sustained hyperphenylalanemia in rats. We have found, however, that in dogs an initial rise in circulating Phe is followed, after a period of time, by a return to normal levels in spite of diet maintenance. PH-ase ws measured in liver samples obtained from dogs before the start of the above diet and at the time when Phe levels returned to normal. It was found that the post-feeding liver sample had 57%-100% less activity than the normal sample. Accordingly, decline in Phe levels cannot be attributed to an increase in PH-ase activity. Experiments are being initiated using labelled Phe, to investigate whether chronic feeding of Phe and p-CPhe resulted in an intestinal block to Phe absorption, which may explain our experimental findings.

摘要

每天给狗喂食含苯丙氨酸(Phe)的持续日粮,并每隔一天喂食对氯苯丙氨酸(p - CPhe),后者是苯丙氨酸羟化酶(PH - 酶)的抑制剂。据报道,这样的日粮会使大鼠产生持续性高苯丙氨酸血症。然而,我们发现,在狗身上,尽管维持日粮不变,但在一段时间后,循环中的苯丙氨酸最初升高之后会恢复到正常水平。在开始上述日粮之前以及苯丙氨酸水平恢复正常时,从狗身上获取肝脏样本并测量PH - 酶。结果发现,喂食后肝脏样本的活性比正常样本低57% - 100%。因此,苯丙氨酸水平的下降不能归因于PH - 酶活性的增加。正在使用标记的苯丙氨酸开展实验,以研究长期喂食苯丙氨酸和对氯苯丙氨酸是否会导致肠道对苯丙氨酸吸收受阻,这可能解释我们的实验结果。

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Res Commun Chem Pathol Pharmacol. 1981 Jul;33(1):145-53.
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