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多胺在小鼠不同肾脏肥大模型中的作用评估。

An evaluation of the role of polyamines in different models of kidney hypertrophy in mice.

作者信息

Tovar A, Sánchez-Capelo A, Cremades A, Peñafiel R

机构信息

Department of Biochemistry and Molecular Biology, School of Medicine, University of Murcia, Spain.

出版信息

Kidney Int. 1995 Sep;48(3):731-7. doi: 10.1038/ki.1995.344.

Abstract

The role of ornithine decarboxylase (ODC) and polyamines in kidney hypertrophy is controversial. Since part of this controversy could be related to differences in the model system used by the different authors, we studied the changes in renal ODC and polyamines in six different models of kidney hypertrophy in mice, including compensatory renal hypertrophy produced by unilateral nephrectomy, experimental diabetes, potassium depletion and treatment with hormones such as testosterone, thyroxine and fluorocortisone. Only in the case of renal hypertrophy produced by testosterone administration was there a significant increase in ODC activity and putrescine content in the kidneys. However, the concomitant treatment with difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, as a 2% solution in the drinking water completely abolished the increase of renal ODC, but the kidney weights increased and other androgenic effects, such as the induction of renal beta-glucuronidase, were not affected. Moreover, DFMO-treatment did not prevent the kidney enlargement produced in other types of hypertrophy, even in the cases associated with hyperplasia. The present results support the premise that, at least in mice, the increase in ODC activity and polyamine biosynthesis is not required for kidney growth, and also that in most cases renal enlargement is not accompanied by any increase in the polyamine content.

摘要

鸟氨酸脱羧酶(ODC)和多胺在肾脏肥大中的作用存在争议。由于这种争议的部分原因可能与不同作者所使用的模型系统差异有关,我们研究了小鼠六种不同肾脏肥大模型中肾脏ODC和多胺的变化,包括单侧肾切除所致的代偿性肾脏肥大、实验性糖尿病、钾缺乏以及用睾酮、甲状腺素和氟氢可的松等激素进行处理。仅在给予睾酮所致的肾脏肥大情况下,肾脏中的ODC活性和腐胺含量有显著增加。然而,用二氟甲基鸟氨酸(DFMO)作为饮用水中2%的溶液进行伴随处理,DFMO是ODC的不可逆抑制剂,它完全消除了肾脏ODC的增加,但肾脏重量增加,且其他雄激素作用,如肾脏β-葡萄糖醛酸酶的诱导,并未受到影响。此外,DFMO处理并不能阻止其他类型肥大中出现的肾脏增大,即使在伴有增生的情况下也是如此。目前的结果支持这样一个前提,即至少在小鼠中,肾脏生长不需要ODC活性和多胺生物合成的增加,而且在大多数情况下,肾脏增大并不伴随多胺含量的任何增加。

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