中国药物警戒 ›› 2026, Vol. 23 ›› Issue (10): 1131-1138.
DOI: 10.19803/j.1672-8629.20260465

• 基础与临床研究 • 上一篇    下一篇

五味子乙素减轻环磷酰胺与表柔比星的心脏毒性研究

支亚婷1, 杨波1, 王皓洁1, 穆泰洋1, 冯雨龙1, 胡开永2, 张敏2, 黄茜2#, 杨华乾1*   

  1. 1苏州大学唐仲英医学研究院,江苏 苏州 215123;
    2荆楚理工学院化工与制药学院,湖北 荆门 448000
  • 收稿日期:2026-06-06 出版日期:2026-10-15 发布日期:2026-10-16
  • 通讯作者: *杨华乾,男,博士,教授,心血管疾病研究。E-mail: hqyang@suda.edu.cn。#为共同通信作者。
  • 作者简介:支亚婷,女,硕士,心血管电生理。
  • 基金资助:
    国家自然科学基金资助项目（82270268）;江苏省双创团队项目（JSSCTD202353）;湖北省重点研发计划项目（2023BCB059）

Schisandrin B attenuates cardiotoxicity induced by cyclophosphamide and epirubicin

Zhi Yating1, Yang Bo1, Wang Haojie1, Mu Taiyang1, Feng Yulong1, Hu Kaiyong2, Zhang Min2, Huang Qian2#, Yang Huaqian1*   

  1. 1Cyrus Tang Medical Institute, Soochow University, Suzhou Jiangsu 215123, China;
    2School of Chemical Engineering and Pharmacy, Jingchu University of Technology, Jingmen Hubei 448000, China
  • Received:2026-06-06 Online:2026-10-15 Published:2026-10-16

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摘要： 目的 探究北五味子重要活性成分五味子乙素减轻环磷酰胺与表柔比星所致的心脏毒性及其剂量效应关系。方法 分别以环磷酰胺与表柔比星建立心脏毒性小鼠模型。每一模型取6~8周龄雄性C57BL/6N小鼠,随机分为5组：对照组、模型组、模型组+低剂量五味子乙素组（10 mg·kg-1·d-1）、模型组+中剂量五味子乙素组（30 mg·kg-1·d-1）、模型组+高剂量五味子乙素组（100 mg·kg-1·d-1）,每组10只小鼠。五味子乙素灌胃给药,每日1次,连续4周;分别腹腔注射环磷酰胺与表柔比星,每周1次,连续4周。采用超声心动图检测左心室射血分数和短轴缩短率,评估左心室收缩功能;检测血清N末端脑钠肽前体（NT-proBNP）和天冬氨酸氨基转移酶（AST）水平;心脏病理切片观察心肌细胞形态学变化,包括空泡化等早期凋亡特征。结果 环磷酰胺模型组与表柔比星模型组小鼠的左心室射血分数及短轴缩短率均显著降低,血清NT-proBNP和AST水平明显升高;心脏整体大小未见明显改变,但均出现显著的心肌细胞空泡化。给予五味子乙素干预后,上述心脏收缩功能指标、血清心肌损伤标志物水平及心肌细胞空泡化程度均明显改善,且改善幅度随五味子乙素剂量增加而增强,呈剂量-效应关系。结论 五味子乙素能剂量依赖性地减轻环磷酰胺与表柔比星所致的心脏毒性,其机制可能与抗氧化应激和抗凋亡有关,提示其作为肿瘤化疗辅助保护剂的潜力。

关键词: 五味子乙素, 环磷酰胺, 表柔比星, 心脏毒性, 剂量效应关系, 氧化应激, 小鼠

Abstract: Objective To investigate the protective effect of Schisandrin B, an important active component of Schisandra chinensis, against cyclophosphamide- and epirubicin-induced cardiotoxicity and to explore its dose-effect relationship. Methods Mouse models of cardiotoxicity were established using cyclophosphamide and epirubicin, respectively. For each model, male C57BL/6N mice aged 6-8 weeks were randomly divided into five groups (n=10 per group): the control group, model group, model + low-dose Schisandrin B group (10 mg·kg-1·d-1), model + medium-dose Schisandrin B group (30 mg·kg-1·d-1), and model + high-dose Schisandrin B group (100 mg·kg-1·d-1). Schisandrin B was administered by oral gavage once daily for 4 consecutive weeks while cyclophosphamide and epirubicin were injected intraperitoneally once weekly for 4 consecutive weeks, respectively. Left ventricular systolic function was evaluated by echocardiography while left ventricular ejection fraction and fractional shortening were observed. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and aspartate aminotransferase (AST) were measured. Cardiac pathological sections were examined for morphological changes in cardiomyocytes, including vacuolization and other early apoptotic features. Results In both the cyclophosphamide model group and the epirubicin model group, left ventricular ejection fraction and fractional shortening were significantly decreased while serum NT-proBNP and AST levels were markedly elevated. No obvious changes in overall heart size were observed, but significant cardiomyocyte vacuolization was present in both models. Following schisandrin B intervention, all the above parameters—cardiac systolic function, serum cardiac injury biomarkers, and the degree of cardiomyocyte vacuolization—were significantly improved. Moreover, improvements increased with the dose of Schisandrin B, which suggested a dose-effect relationship. Conclusion Schisandrin B can dose-dependently attenuate cyclopho-sphamide- or epirubicin-induced cardiotoxicity, potentially through such mechanisms as anti-oxidative stress and inhibition of apoptosis, suggesting its potential to be used as an adjunctive cardioprotective agent during cancer chemotherapy.

Key words: Schisandrin B, Cyclophosphamide, Epirubicin, Cardiotoxicity, Dose-Effect Relationship, Oxidative Stress, Mice

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