矿物质皮质激素受体阻断胆管结扎后上皮 Na+ 通道活化

IF 10.3 1区 医学 Q1 UROLOGY & NEPHROLOGY Journal of The American Society of Nephrology Pub Date : 2024-11-01 Epub Date: 2024-07-10 DOI:10.1681/ASN.0000000000000442
Xue-Ping Wang, Stephanie M Mutchler, Rolando Carrisoza-Gaytan, Andrew J Nickerson, Catherine J Baty, Mohammad Al-Bataineh, Amber Vandevender, Tetsuji Morimoto, Priyanka Srinivasan, Roderick J Tan, Michael J Jurczak, Lisa M Satlin, Ossama B Kashlan
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引用次数: 0

摘要

背景:肝病患者的钠和液体潴留通常被认为是有效循环容量减少和肾素-血管紧张素-醛固酮系统(RAAS)受刺激所致。然而,有证据表明,没有 RAAS 激活的患者也会出现体液潴留,这表明还有其他机制参与其中。在体外,胆汁酸会激活醛固酮敏感性远端肾小球中的上皮 Na+ 通道(ENaC)。如果这种情况发生在体内,那么即使醛固酮信号被拮抗,ENaC也可能在肝病中被激活:为了验证这一点,我们对小鼠进行胆管结扎以诱发肝病,并增加循环胆汁酸,同时给予螺内酯以拮抗醛固酮信号传导。我们分析了血液、尿液和身体成分的影响。我们还测定了牛胆酸(一种在肝病中升高的主要共轭胆酸)对微灌注兔集合管中离子通量的影响:结果:与假结扎相比,胆管结扎增加了苯扎米尔敏感性利尿,表明ENaC被激活。对ENaC表达、裂解或定位的影响无法解释这些效应。胆管结扎小鼠比假手术小鼠获得的液体也明显更多。阻断ENaC可逆转胆管结扎小鼠的液体增加,但对假手术小鼠没有影响。在解剖的兔子集合管中,表达 ENaC 的牛磺胆酸刺激了 Na+ 的净吸收:我们的研究结果为肝病患者钠和液体潴留的一种新型醛固酮依赖性机制提供了实验证据。
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Epithelial Na + Channel Activation after Bile Duct Ligation with Mineralocorticoid Receptor Blockade.
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来源期刊
Journal of The American Society of Nephrology
Journal of The American Society of Nephrology 医学-泌尿学与肾脏学
CiteScore
22.40
自引率
2.90%
发文量
492
审稿时长
3-8 weeks
期刊介绍: The Journal of the American Society of Nephrology (JASN) stands as the preeminent kidney journal globally, offering an exceptional synthesis of cutting-edge basic research, clinical epidemiology, meta-analysis, and relevant editorial content. Representing a comprehensive resource, JASN encompasses clinical research, editorials distilling key findings, perspectives, and timely reviews. Editorials are skillfully crafted to elucidate the essential insights of the parent article, while JASN actively encourages the submission of Letters to the Editor discussing recently published articles. The reviews featured in JASN are consistently erudite and comprehensive, providing thorough coverage of respective fields. Since its inception in July 1990, JASN has been a monthly publication. JASN publishes original research reports and editorial content across a spectrum of basic and clinical science relevant to the broad discipline of nephrology. Topics covered include renal cell biology, developmental biology of the kidney, genetics of kidney disease, cell and transport physiology, hemodynamics and vascular regulation, mechanisms of blood pressure regulation, renal immunology, kidney pathology, pathophysiology of kidney diseases, nephrolithiasis, clinical nephrology (including dialysis and transplantation), and hypertension. Furthermore, articles addressing healthcare policy and care delivery issues relevant to nephrology are warmly welcomed.
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