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全氟癸酸对大鼠心脏的影响。

The effects of perfluoro-n-decanoic acid in the rat heart.

作者信息

Pilcher G D, Langley A E

出版信息

Toxicol Appl Pharmacol. 1986 Sep 30;85(3):389-97. doi: 10.1016/0041-008x(86)90346-7.

Abstract

Perfluoro-n-decanoic acid (PFDA) is a synthetic chemical resembling a 10-carbon fatty acid. Several studies have suggested that the toxic mechanism of PFDA may involve impaired lipid metabolism and/or altered cell membrane function. We examined the possibility that altered cell membrane structure in the heart might lead to changes in the functional activity of the organ. Functional characteristics were determined in the isolated perfused rat heart by measuring the ability of the heart to respond to either sympathetic nerve stimulation or infused norepinephrine. PFDA reduced the intrinsic resting heart rate and the inotropic response to a stimulus with maximal effects occurring 8 days after dosing. In addition, resting heart rate measured in vivo was found to be reduced in PFDA-treated rats 6 to 8 days after dosing. beta-Receptor binding studies conducted 8 days after a single dose of PFDA showed that the maximum binding capacity was reduced by PFDA treatment without significant changes in receptor affinity. It is concluded that the reduction in the inotropic response to catecholamines following PFDA treatment may be explained in part by lower beta-receptor density in the myocardial cell membrane. These effects may be related to the early fall in serum thyroid hormone levels as previously reported.

摘要

全氟正癸酸(PFDA)是一种类似含10个碳原子脂肪酸的合成化学品。多项研究表明,PFDA的毒性机制可能涉及脂质代谢受损和/或细胞膜功能改变。我们研究了心脏细胞膜结构改变可能导致器官功能活动变化的可能性。通过测量心脏对交感神经刺激或注入去甲肾上腺素的反应能力,在离体灌注大鼠心脏中确定功能特征。PFDA降低了固有静息心率和对刺激的变力反应,给药后8天出现最大效应。此外,在给药后6至8天,发现PFDA处理的大鼠体内测量的静息心率降低。单次给予PFDA 8天后进行的β受体结合研究表明,PFDA处理降低了最大结合能力,而受体亲和力没有显著变化。得出的结论是,PFDA处理后对儿茶酚胺变力反应的降低可能部分归因于心肌细胞膜中β受体密度降低。这些影响可能与先前报道的血清甲状腺激素水平早期下降有关。

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