秋水仙碱通过抑制 P53 依赖性细胞凋亡防止心肌梗死小鼠心脏破裂

IF 1.2 4区 医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS
Liang Shen, Shaodai Huang, Hongyan Fan, Changlin Zhai
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引用次数: 0

摘要

心脏破裂是心肌梗死(MI)后的致命并发症,目前还没有有效的药物策略来预防这种情况。在这项研究中,我们探讨了秋水仙碱对小鼠心肌梗死后心脏破裂的影响及其内在机制。我们通过永久性结扎左前降支动脉诱发小鼠心肌梗死,并在心肌梗死后第1天至第7天以0.1毫克/千克/天的剂量口服秋水仙碱或载体。培养的新生心肌细胞和成纤维细胞暴露在常氧或缺氧环境中,并接受秋水仙碱处理。心肌梗死后 1 周,秋水仙碱显著提高了存活率(秋水仙碱,n = 46:82.6% 对车辆,n = 42:61.9%,P < 0.05)。组织学分析表明,秋水仙碱能明显缩小梗塞面积,减少梗塞区周围巨噬细胞的数量。通过 TUNEL 检测,秋水仙碱可减少边界区心肌细胞以及培养的心肌细胞和成纤维细胞的凋亡。秋水仙碱通过抑制细胞凋亡防止心脏破裂,这归因于它下调了 p53 的活性。我们的研究结果表明,秋水仙碱可能是一种预防心脏破裂的前瞻性药物,但还需要进行大规模的临床试验。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Colchicine Prevents Cardiac Rupture in Mice with Myocardial Infarction by Inhibiting P53-Dependent Apoptosis

Cardiac rupture is a fatal complication following myocardial infarction (MI) and there are currently no effective pharmacological strategies for preventing this condition. In this study, we investigated the effect of colchicine on post-infarct cardiac rupture in mice and its underlying mechanisms.

We induced MI in mice by permanently ligating the left anterior descending artery. Oral colchicine or vehicle was administered at a dose of 0.1 mg/kg/day from day 1 to day 7 after MI. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with colchicine.

Colchicine significantly improved the survival rate (colchicine, n = 46: 82.6% versus vehicle, n = 42: 61.9%, P < 0.05) at 1 week after MI. Histological analysis revealed colchicine significantly reduced the infarct size and the number of macrophages around the infarct area. Colchicine decreased apoptosis in the myocardium of the border zone and cultured cardiomyocytes and fibroblasts as assessed by TUNEL assay. Colchicine also attenuated the activation of p53 and decreased the expression of cleaved-caspase 3 and bax, as assessed by Western blotting.

Colchicine prevents cardiac rupture via inhibition of apoptosis, which is attributable to the downregulation of p53 activity. Our findings suggest that colchicine may be a prospective preventive medicine for cardiac rupture, however, large clinical trials are required.

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来源期刊
International heart journal
International heart journal 医学-心血管系统
CiteScore
2.50
自引率
6.70%
发文量
148
审稿时长
6-12 weeks
期刊介绍: Authors of research articles should disclose at the time of submission any financial arrangement they may have with a company whose product figures prominently in the submitted manuscript or with a company making a competing product. Such information will be held in confidence while the paper is under review and will not influence the editorial decision, but if the article is accepted for publication, the editors will usually discuss with the authors the manner in which such information is to be communicated to the reader.
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