2026 年第 3 期 第 21 卷

补体因子D抑制剂Danicopan改善心肌梗死后小鼠心室重构研究

Study on complement factor D inhibitor Danicopan ameliorating ventricular remodeling in mice after myocardial infarction

作者：靳姝慧邵怡辉张聪聪

英文作者：Jin Shuhui Shao Yihui Zhang Congcong

单位：首都医科大学附属北京安贞医院北京市心肺血管疾病研究所心血管基础与转化医学研究中心，北京100029

英文单位：Research Center of Basic and Translational Cardiovascular Medicine Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University Beijing 100029 China

关键词：心肌梗死；补体因子D；Danicopan；纤维化；心功能

英文关键词：Myocardialinfarction;ComplementfactorD;Danicopan;Fibrosis;Cardiacfunction

• 摘要：

• 目的 探讨补体因子D（CFD）抑制剂Danicopan对心肌梗死后小鼠心功能、心肌肥大及心肌纤维化的影响。方法 C57BL/6小鼠完全随机分为假手术组、MI对照组和MI+Danicopan组。通过结扎左冠状动脉前降支构建心肌梗死模型。术后当天起，MI+Danicopan组腹腔注射Danicopan（10 mg/kg），MI对照组则注射等容积的磷酸盐缓冲液，每周给药2次，持续3周。假手术组仅进行开胸操作而不结扎左冠状动脉前降支，不给药。干预结束后，行超声心动图评估心功能；取心脏组织进行小麦胚芽凝集素染色观察心肌细胞横截面积，Masson三色染色分析胶原沉积并计算纤维化面积百分比。结果 MI对照组小鼠左心室射血分数（LVEF）和左心室短轴缩短率（LVFS）显著低于假手术组［（21.3±1.7）%比（68.3±2.4）%、（9.5±1.0）%比（40.7±3.9）%］，但MI+Danicopan给药组小鼠的LVEF和LVFS［（46.2±12.3）%,（23.0±7.3）%］均显著高于MI对照组（均P<0.05）。病理学观察检测表明，Danicopan给药可显著减轻心肌梗死导致的心肌细胞肥大程度，降低心肌组织整体胶原容积分数。结论 CFD抑制剂Danicopan可显著改善心肌梗死模型小鼠心功能，减轻心肌细胞病理性肥大和间质纤维化，提示其可能作为治疗心肌梗死后心室重构的潜在药物。

• Objective To investigate the effects of Danicopan, a complement factor D (CFD) inhibitor, on cardiac function, myocardial hypertrophy and myocardial fibrosis in mice after myocardial infarction （MI）. Methods C57BL/6 mice were randomly divided into sham operation group, MI control group and MI+Danicopan group. MI model was established by ligating the left anterior descending coronary artery. From the day of operation, mice in the MI+Danicopan group were intraperitoneally injected with Danicopan (10 mg/kg), while those in the MI control group were injected with an equal volume of phosphate-buffered saline, twice a week for 3 consecutive weeks. Mice in the sham operation group only received thoracotomy without ligation of the left anterior descending coronary artery and no drug administration. After the intervention, echocardiography was performed to evaluate cardiac function. Cardiac tissues were collected for wheat germ agglutinin staining to observe the cross-sectional area of cardiomyocytes, and Masson′s trichrome staining to analyze collagen deposition and calculate the percentage of fibrotic area. Results The left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) in the MI control group were significantly lower than those in the sham operation group ［(21.3±1.7)% vs (68.3±2.4)%, (9.5±1.0)% vs (40.7±3.9)%］, while the LVEF and LVFS in the MI+Danicopan group ［(46.2±12.3)%, (23.0±7.3)%］ were significantly higher than those in the MI control group (all P<0.05). Pathological observations showed that Danicopan administration could significantly alleviate the degree of cardiomyocyte hypertrophy induced by MI and reduce the overall collagen volume fraction of myocardial tissue. Conclusion Danicopan, a CFD inhibitor, can significantly improve cardiac function, and alleviate pathological cardiomyocyte hypertrophy and interstitial fibrosis in mice with MI, suggesting that it may serve as a potential drug for the treatment of ventricular remodeling after MI.