Study on the Impact of Kangxiyixin Formula on Ventricular Remodeling in Mice with Dilated Cardiomyopathy via the Sirt1/P53/Drp1 Axis postprint

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.