Laboratory Animal Science ›› 2025, Vol. 42 ›› Issue (3): 59-65.DOI: 10. 3969 / j. issn. 1006-6179. 2025. 03. 009

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Protective Effect of Dicoumarol on Pathological Cardiac Hypertrophy Induced by Stress Overload

  

  1. ( 1. Taikang Medical School( Basic Medical Sciences) of Wuhan University, Wuhan 430071,China)
    ( 2. Department of Cardiology, Zhongnan Hospital, Wuhan University, Wuhan 430071, China)
    ( 3. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060,China)
  • Received:2024-04-16 Online:2025-06-28 Published:2025-07-05

双香豆素对压力超负荷诱导的病理性心肌肥厚的保护作用

  

  1. ( 1. 武汉大学泰康医学院(基础医学院) ,武汉 430071) ( 2. 武汉大学中南医院心血管内科, 武汉 430071)
    ( 3. 武汉大学人民医院心血管内科,武汉 430060)
  • 通讯作者: 张鹏( 1984—) ,博士,教授,研究方向为代谢疾病和非酒精性脂肪肝,E-mail:zhp@ whu. edu. cn
  • 作者简介:周思懿( 1998—) ,硕士,研究方向为心肌肥厚,E-mail:liwei111@ whu. edu. cn
  • 基金资助:
    国家自然基金委面上项目( 81970011) 。

Abstract:

Objective This study aimed to investigate the protective effects of dicoumarol on pathological cardiac hypertrophy induced by stress overload, thus providing scientific evidence for its potential therapeutic role. Methods We established pathological cardiac hypertrophy models in vitro using primary cardiomyocytes and in vivo using mice, administering dicoumarol and evaluating its protective effects against cardiac hypertrophy. Isoproterenol stimulation was employed to induce cardiomyocyte hypertrophy in the primary cell culture. The cells were categorized into control and treatment groups. Immunofluorescence staining was conducted after 24 hours of stimulation to evaluate cellular area. In the mouse model, pathological cardiac hypertrophy was induced via aortic constriction. Mice were divided into solvent control and treatment groups, with each group comprising 9 mice. The treatment group received dicoumarol at a dosage of 10 mg / kg every day. Four weeks post-surgery, cardiac structure and function were evaluated using echocardiography, while the degree of cardiac hypertrophy and fibrosis was  assessed via histopathological staining. Results In the in vitro model, dicoumarol significantly attenuated isoproterenol-induced cardiomyocyte hypertrophy.In the mouse model of myocardial hypertrophy, dicoumarol administration markedly ameliorated pressure overload-induced cardiac dysfunction, myocardial hypertrophy, and fibrosis compared to the solvent control group. Conclusion Dicoumarol exhibits protective effects against pressure overload-induced pathological myocardial hypertrophy and fibrosis, thereby improving cardiac function.

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摘要:

目的 探讨双香豆素对于压力超负荷诱导的病理性心肌肥厚的保护作用,为保护病理性心肌肥厚提供科学依据。 方法 分别在体外原代心肌细胞和体内小鼠中建立病理性心肌肥厚模型,给予双香豆素并评价其在心肌肥厚中的保护作用。 原代心肌细胞用苯肾上腺素刺激构建心肌细胞肥大模型,分为对照组和给药组,体外刺激 24 h后用免疫荧光染色法评估细胞面积。 小鼠采用主动脉弓缩窄术建立病理性心肌肥厚模型,分为溶剂对照组和给药组,每组 9 只小鼠,给药组以每天 10 mg / kg 使用双香豆素给药,术后 4 周超声检测心脏结构和功能,并通过病理染色评价心肌肥厚和纤维化的程度。 结果 在体外细胞模型中,双香豆素给药后显著减轻苯肾上腺素刺激导致的心肌细胞肥大。 在小鼠心肌肥厚模型中,与溶剂对照组比较,双香豆素显著减轻压力负荷诱导的心脏功能受损、心肌肥厚和心脏纤维化。 结论双香豆素能够保护压力负荷导致的病理性心肌肥厚和心肌纤维化,改善心脏功能。

关键词: 双香豆素, 心肌肥厚, 心脏功能

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