血液透析诱发心肌梗死大鼠模型中的线粒体功能障碍和离子失衡

IF 3.9 3区 工程技术 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Biomedicines Pub Date : 2024-10-20 DOI:10.3390/biomedicines12102402
Yuxin Nie, Liyu Lin, Qiang Yang, Jiachang Hu, Minmin Sun, Fangfang Xiang, Xuesen Cao, Jinbo Yu, Yaqiong Wang, Jie Teng, Xiaoqiang Ding, Bo Shen, Zhen Zhang
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引用次数: 0

摘要

背景/目的:血液透析诱发的心肌震颤(HIMS)是接受维持性血液透析的患者经常出现的一种并发症,其特点是缺血发作导致短暂的左心室功能障碍。线粒体功能障碍以及钾(K+)和钙(Ca2+)等关键离子的波动与 HIMS 的发病机制有关。本研究旨在探讨线粒体功能障碍的作用以及线粒体 ATP 敏感性钾通道(mitoKATP)在缓解 HIMS 中的保护潜力。研究方法建立 5/6 肾切除大鼠模型,以模拟慢性肾病和随后的 HIMS。通过在血液透析前给大鼠注射线粒体KATP开启剂重氮氧化物(DZX)和线粒体KATP阻断剂5-羟基癸酸酯(5-HD)来评估线粒体KATP通道调节剂的作用。线粒体功能通过测量膜电位、ATP合酶活性和线粒体内Ca2+水平进行评估。使用斑点追踪超声心动图评估心肌功能。结果接受血液透析的大鼠左心室应变和同步性显著降低。与对照组相比,服用 DZX 能明显改善线粒体功能并降低心肌应变。相反,5-HD 会加重线粒体肿胀并破坏心肌功能。透析液中较高的 K+ 和 Ca2+ 浓度与线粒体能量代谢和心肌应变的改善有关。结论血液透析过程中线粒体功能障碍和离子失衡是导致 HIMS 的关键因素。激活线粒体 KATP 通道可提供线粒体保护,并可作为缓解 HIMS 的潜在治疗策略。
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Mitochondrial Dysfunction and Ion Imbalance in a Rat Model of Hemodialysis-Induced Myocardial Stunning.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K+) and calcium (Ca2+) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoKATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoKATP channel modulators were evaluated by administering diazoxide (DZX), a mitoKATP opener, and 5-hydroxydecanoate (5-HD), a mitoKATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca2+ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K+ and Ca2+ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoKATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

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来源期刊
Biomedicines
Biomedicines Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
5.20
自引率
8.50%
发文量
2823
审稿时长
8 weeks
期刊介绍: Biomedicines (ISSN 2227-9059; CODEN: BIOMID) is an international, scientific, open access journal on biomedicines published quarterly online by MDPI.
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