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离体灌流小鼠肾上腺模型——一种研究醛固酮分泌的新模型。

The ex vivo perfused mouse adrenal gland-a new model to study aldosterone secretion.

机构信息

Medical Cell Biology, University of Regensburg, Regensburg, Germany.

出版信息

Pflugers Arch. 2024 Jun;476(6):911-922. doi: 10.1007/s00424-024-02950-z. Epub 2024 Mar 28.

DOI:10.1007/s00424-024-02950-z
PMID:38538989
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11139715/
Abstract

Aldosterone is a steroid hormone that is important for maintaining the volume and ionic composition of extracellular fluids and is produced in the zona glomerulosa of the adrenal cortex. The basic mechanisms controlling aldosterone secretion are known. However, more detailed studies on the regulation of aldosterone secretion often fail due to the lack of suitable models: although secretion can be studied in cultured adrenocortical cells under defined conditions, the differentiation status of the cells is difficult to control and the complex anatomy of the adrenal cortex is lost. In living animals, the physiological context is intact, but the influences are manifold and the examination conditions cannot be sufficiently controlled. One method that closes the gap between cell models and studies in living animals is the isolated perfused adrenal gland. In the past, this method has provided important data on the pathophysiology of adrenal glands from larger animals, but the technique was not used in mice. Here, we developed a method for isolation and perfusion of the mouse adrenal gland to study aldosterone secretion. This technique preserves the complex anatomical and functional context of the mouse adrenal cortex, to ensure defined experimental conditions and to minimize extra-adrenal influences. Initial series of experiments with the ex vivo perfused mouse adrenal gland show that this model offers the possibility for unique insights into pathophysiological regulatory principles and is suitable for the use of genetically modified mouse models.

摘要

醛固酮是一种类固醇激素,对于维持细胞外液的容量和离子组成非常重要,它在肾上腺皮质的球状带中产生。控制醛固酮分泌的基本机制是已知的。然而,由于缺乏合适的模型,对醛固酮分泌的更详细的调节研究经常失败:尽管可以在特定条件下培养的肾上腺皮质细胞中研究分泌,但细胞的分化状态难以控制,而且肾上腺皮质的复杂解剖结构也丢失了。在活体动物中,生理环境是完整的,但影响是多样的,检查条件不能得到充分控制。一种在细胞模型和活体动物研究之间架起桥梁的方法是分离灌注的肾上腺。过去,这种方法为来自较大动物的肾上腺的病理生理学提供了重要数据,但该技术未在小鼠中使用。在这里,我们开发了一种分离和灌注小鼠肾上腺的方法来研究醛固酮的分泌。该技术保留了小鼠肾上腺皮质的复杂解剖和功能背景,以确保明确的实验条件并最小化肾上腺外的影响。用离体灌注的小鼠肾上腺进行的初步实验系列表明,该模型为深入了解病理生理调节原理提供了可能性,并且适合使用基因修饰的小鼠模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/e011e49365b6/424_2024_2950_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/dab4c492f2b4/424_2024_2950_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/c7aa5b9bfa27/424_2024_2950_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/014fc996982c/424_2024_2950_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/8c9c134b520e/424_2024_2950_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/40b4b8389a67/424_2024_2950_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/e011e49365b6/424_2024_2950_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/dab4c492f2b4/424_2024_2950_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/c7aa5b9bfa27/424_2024_2950_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/014fc996982c/424_2024_2950_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/8c9c134b520e/424_2024_2950_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/40b4b8389a67/424_2024_2950_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6ed6/11139715/e011e49365b6/424_2024_2950_Fig6_HTML.jpg

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本文引用的文献

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Int J Mol Sci. 2022 Nov 19;23(22):14388. doi: 10.3390/ijms232214388.
2
Online Detection of Catecholamine Release from the Perfused Rat Adrenal Gland.灌注大鼠肾上腺中儿茶酚胺释放的在线检测
Methods Mol Biol. 2023;2565:91-103. doi: 10.1007/978-1-0716-2671-9_7.
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Genetics of Primary Aldosteronism.原发性醛固酮增多症的遗传学。
Hypertension. 2022 May;79(5):887-897. doi: 10.1161/HYPERTENSIONAHA.121.16498. Epub 2022 Feb 10.
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Primary aldosteronism.原发性醛固酮增多症。
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The inferior phrenic arteries: A systematic review and meta-analysis.膈下动脉:一项系统评价与荟萃分析
Ann Anat. 2021 May;235:151679. doi: 10.1016/j.aanat.2021.151679. Epub 2021 Jan 29.
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Ion Channel Function and Electrical Excitability in the Zona Glomerulosa: A Network Perspective on Aldosterone Regulation.肾小球带中的离子通道功能与电兴奋性:醛固酮调节的网络视角
Annu Rev Physiol. 2021 Feb 10;83:451-475. doi: 10.1146/annurev-physiol-030220-113038. Epub 2020 Nov 11.
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Nat Rev Endocrinol. 2020 Oct;16(10):578-589. doi: 10.1038/s41574-020-0382-4. Epub 2020 Jul 28.
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