比格犬模型中慢性肾功能不全合并房颤对左心房内皮功能的影响
Effects of Chronic Renal Insufficiency Combined with Atrial Fibrillation on Left Atrial Endothelial Function in a Beagle Model.
Effects of Chronic Renal Insufficiency Combined with Atrial Fibrillation on Left Atrial Endothelial Function in a Beagle Model.
心房颤动(AF)与肾功能不全(RI)的共存是一种高患病率的临床复杂现象。本研究探讨了慢性中度肾功能不全合并心房颤动对比格犬左心房内皮功能的影响。采用明胶海绵颗粒经导管栓塞左肾动脉主干诱导慢性肾功能不全,动物维持3个月以促使慢性肾实质损伤形成。随后通过持续快速心房起搏(基础周期长度60 ms;电压为舒张期起搏阈值的4倍;持续180分钟)诱导心房颤动。采用苏木精-伊红染色评估组织学改变。采用酶联免疫吸附试验、实时定量聚合酶链反应和蛋白质印迹法检测血浆及心脏组织中与内皮功能、凝血、纤溶、炎症及肾素-血管紧张素-醛固酮系统(RAAS)活性相关的参数。结果表明,成功建立了中度肾功能不全的慢性肾损伤模型,并经血浆肌酐、尿素氮显著升高及肌酐清除率降低所证实。合并肾功能不全与心房颤动的比格犬左心房内皮功能显著受损,并伴有促凝血效应增强和纤溶功能下降。炎症标志物在肾功能不全操作或心房颤动诱导后升高,并在肾功能不全合并心房颤动组中进一步升高。此外,以肾素和醛固酮水平升高为证据的RAAS活性在肾功能不全后升高,并与心房颤动联合后进一步增强。总之,本研究成功建立了比格犬慢性中度肾功能不全合并心房颤动的在体动物模型,证明该合并状态显著扰乱了左心房内皮功能并增加了血栓形成风险。
The co-occurrence of atrial fibrillation (AF) and renal insufficiency (RI) represents a clinically complex phenomenon with high prevalence. This study investigated the impact of chronic moderate RI combined with AF on left atrial endothelial function in beagles. Chronic RI was induced by transcatheter embolization of the main branch of the left renal artery using gelatin sponge granules, with animals maintained for 3 months to allow chronic renal parenchymal damage to develop. AF was subsequently induced by continuous rapid atrial pacing (basic cycle length, 60 ms; voltage, 4 times the diastolic pacing threshold; 180 min). Histological changes were assessed using hematoxylin and eosin staining. Parameters associated with endothelial function, coagulation, fibrinolysis, inflammation, and renin-angiotensin-aldosterone system (RAAS) activity in plasma and heart tissues were examined using enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction, and western blotting. The results demonstrated successful establishment of a chronic kidney damage model with moderate RI, confirmed by significantly elevated plasma creatinine, urea nitrogen, and reduced creatinine clearance. Left atrial endothelial function was significantly impaired in beagles with combined RI and AF, accompanied by enhanced procoagulant effects and decreased fibrinolysis. Inflammatory markers were elevated following the RI procedure or AF induction and were further enhanced in the combined RI+AF group. Additionally, RAAS activity, evidenced by increased renin and aldosterone levels, was elevated following RI and further augmented upon combination with AF. In summary, this study successfully established an in vivo animal model of chronic moderate RI combined with AF in beagles, demonstrating that this combination significantly disturbed left atrial endothelial function and increased thrombotic risk.
Yan Yin, Fukun Chen, Lifeng Liu, Jian Li, Xu Liu, Zhipeng Hu, et al. Effects of Chronic Renal Insufficiency Combined with Atrial Fibrillation on Left Atrial Endothelial Function in a Beagle Model.. Journal of visualized experiments : JoVE. 2026; doi:10.3791/70271.
Yan Yin, Fukun Chen, Lifeng Liu, Jian Li, Xu Liu, Zhipeng Hu, et al (2026). Effects of Chronic Renal Insufficiency Combined with Atrial Fibrillation on Left Atrial Endothelial Function in a Beagle Model.. Journal of visualized experiments : JoVE. https://doi.org/10.3791/70271
Yan Yin, Fukun Chen, Lifeng Liu, Jian Li, Xu Liu, Zhipeng Hu, et al. Effects of Chronic Renal Insufficiency Combined with Atrial Fibrillation on Left Atrial Endothelial Function in a Beagle Model.[J]. Journal of visualized experiments : JoVE, 2026 doi:10.3791/70271.
翻译全文 · AI 文献问答 · PDF 原文下载 · 引用导出