Abstract: Background　The Kangxiyixin formula，used clinically for dilated cardiomyopathy（DCM），has shown potential in curbing ventricular remodeling and enhancing cardiac function in prior studies，yet its mechanisms remain elusive. This study aims to underpin its clinical application through experimental evidence. Objective　To explore the impact of the Kangxiyixin formula on ventricular remodeling in DCM mice via the Sirt1（sirtuin 1）/P53/Drp1（dynamin-related protein 1） axis. Methods　Thirty cTnTR141W transgenic mice were randomly divided into model，Kangxiyixin formula，and Captopril groups（10 each），with 10 C57BL/6J mice as the normal control. After 8 weeks of drug intervention，echocardiography assessed left ventricular end-systolic diameter（LVESD），left ventricular end-diastolic diameter（LVEDD），left ventricular fractional shortening（LVFS），and left ventricular ejection fraction（LVEF）. Hematoxylin-eosin（HE）and Masson staining evaluated myocardial pathology and fibrosis. Transmission electron microscopy examined mitochondrial ultrastructure. Real-Time PCR measured Sirt1，P53，and Drp1 mRNA levels in myocardial tissue，while Western Blot analyzed their protein levels，including acetylated P53（a-P53）. Results　Echocardiography and heart weight measurements revealed higher LVEDD and heart weight，but lower LVEF and LVFS in the model group versus normal（P<0.05）. The Kangxiyixin formula and Captopril groups showed improved LVEF and LVFS，and reduced heart weight compared to the model group（P<0.05）. HE and Masson staining indicated disordered myocyte arrangement，hypertrophy，and significant fibrosis in the model group，with marked mitochondrial injury. The treatment groups exhibited better-structured myocardium，less collagen deposition，and reduced fibrosis. Transmission electron microscopy showed normal left ventricular wall ultrastructure in the normal group，but damage and mitochondrial swelling in the model group. The treatment groups had improved ultrastructure and mitochondrial morphology. Real-Time PCR found lower Sirt1 mRNA and higher Drp1 and P53 mRNA in the model group than normal（P<0.05）. The treatment groups had higher Sirt1 and lower Drp1，P53 mRNA than the model group（P<0.05）. Western Blot showed lower Sirt1 protein and higher Drp1 and aP53/P53 ratio in the model group than normal（P<0.05），with opposite results in the treatment groups. Conclusion　The Kangxiyixin formula improves cardiac function and inhibits ventricular remodeling in cTnTR141W transgenic mice，likely through upregulating Sirt1 expression and downregulating P53 acetylation and Drp1 levels.

Key words: Cardiomyopathy, dilated；Dilated cardiomyopathy；Ventricular remodeling；Kangxiyixin formula；Sirtuin 1；P53；Dynamin-related protein 1

摘要： 背景　抗纤益心方是临床治疗扩张型心肌病的经验方，前期研究抗纤益心方能够抑制扩张型心肌病心室重构，改善心脏功能作用，但作用机制尚不清楚。本研究为临床应用抗纤益心方提供实验依据。目的　基于沉默信息调节因子2相关酶1（Sirt1）/P53/动力蛋白相关蛋白1（Drp1）轴探讨抗纤益心方对扩张型心肌病（DCM）小鼠心室重构的影响。方法　30只cTnTR141W转基因小鼠随机分为模型组、抗纤益心方组、卡托普利组，每组10只，另设10只C57BL/6J小鼠为正常组，药物干预8周。超声心动图检测小鼠心脏左室收缩末期内径（LVESD）、左室舒张末期内径（LVEDD）、左室缩短分数（LVFS）、左室射血分数（LVEF）；苏木素-伊红（HE）染色、Masson染色观察小鼠心肌组织病理学改变及心肌纤维化情况；透射电镜观察线粒体超微结构；Real-Time PCR测定小鼠心肌组织中Sirt1、P53、Drp1 mRNA水平；免疫印迹（Western Blot）检测心肌组织中Sirt1、P53、乙酰化的P53（a-P53）、Drp1蛋白水平。结果　超声心动图检查及称量心脏重量结果示，模型组小鼠LVEDD、心脏重量较正常组升高，LVEF、LVFS较正常组降低（P<0.05）；抗纤益心方组LVEF、LVFS较模型组升高，心脏重量较模型组降低（P<0.05）；卡托普利组LVEF、LVFS较模型组升高，LVEDD、心脏重量较模型组降低（P<0.05）；HE染色与Masson染色结果表明，模型组心肌细胞排列紊乱，呈不同程度肥大，纤维化明显，心肌线粒体超微结构损伤明显；与模型组比较，抗纤益心方组及卡托普利组心肌组织整体结构相对规则，排列较为密集，心肌细胞间隙的胶原蛋白沉积及纤维化水平显著降低。透射电镜观察结果可见，正常组左心室壁心肌超微结构正常，模型组心肌超微结构明显破坏，线粒体肿胀明显；抗纤益心方组和卡托普利组心肌超微结构损伤得到明显改善，线粒体形态有所恢复。Real-Time PCR结果示，模型组Sirt1 mRNA相对表达量低于正常组，Drp1、P53 mRNA相对表达量高于正常组（P<0.05）；抗纤益心方组、卡托普利组Sirt1 mRNA相对表达量高于模型组，Drp1、P53 mRNA相对表达量低于模型组（P<0.05）。Western Blot检测结果示模型组Sirt1蛋白表达低于正常组，Drp1蛋白、aP53/P53高于正常组（P<0.05）；抗纤益心方组、卡托普利组Sirt1蛋白表达高于模型组，Drp1蛋白、aP53/P53低于模型组（P<0.05）。结论　抗纤益心方能改善cTnTR141W转基因小鼠心功能，抑制心室重构，其机制可能与升高Sirt1 mRNA及蛋白表达水平，抑制P53的乙酰化与Drp1 mRNA及蛋白表达水平有关。

关键词: 心肌病, 扩张型；扩张型心肌病；心室重构；抗纤益心方；沉默信息调节因子 2 相关酶 1；P53；动力蛋白相关蛋白1