OBJECTIVE To investigate the effects and underlying mechanisms of Yiqi Huoxue Decoction (YQHX) on mitochondrial midzone division and peripheral fission in myocardial tissue after myocardial infarction (MI).

METHODS A total of 48 male SPF-grade C57BL/6N mice were randomly divided into a sham-operated group (Sham, n=12) and a left anterior descending coronary artery ligation MI model (n=36). After MI surgery, mice deemed to have successfully developed the model were randomly divided into a model group (MI, n=12), a YQHX group (n=12), and an empagliflozin group (EMPA, n=12) based on echocardiographic results. Four weeks after infarction, cardiac function and structural changes were comprehensively evaluated using echocardiography imaging, serum myocardial injury biomarkers, and hematoxylin-eosin (HE) staining. Transmission electron microscopy (TEM) was employed to observe mitochondrial ultrastructural, morphological, and quantitative changes at the peri-infarct zone. Myocardial mitochondria and cytoplasmic fractions were isolated from myocardial tissue using a mitochondrial extraction kit, and the spatial expression changes of mitochondrial fission-related proteins in both mitochondria and cytoplasm of the peri-infarct myocardium were analyzed by Western blot. These proteins included dynamin-related protein 1 (Drp1), its phosphorylated form at serine 616 (P-Drp1-Ser616), mitochondrial fission factor (MFF), and mitochondrial fission protein 1 (Fis1).

RESULTS Compared with the MI group, mice in the YQHX group exhibited significantly increased left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) (P < 0.000 1), as well as decreased left ventricular internal dimension-diastole (LVIDd) and left ventricular end-systolic diameter (LVIDs) (P < 0.05, P < 0.01), suggesting improved cardiac function. Additionally, serum levels of lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) were significantly reduced in the YQHX group (P < 0.05, P < 0.001), indicating cardio-protective effects of YQHX against ischemic injury. HE staining showed that YQHX improved cellular morphology, suggesting structural improvement. TEM showed that YQHX significantly improved mitochondrial swelling and reduced mitochondrial fragmentation in the marginal zone of myocardial infarction, thereby preserving mitochondrial ultrastructure. Furthermore, Western blot showed that YQHX treatment significantly downregulated P-Drp1-Ser616 expression (P < 0.05) in the cytoplasm. Interestingly, YQHX treatment significantly downregulated mitochondrial Fis1 expression (P < 0.05), thereby inhibiting peripheral mitochondrial fission. Meanwhile, YQHX treatment significantly increased MFF expression in mitochondria (P < 0.01), which may promote mitochondrial midzone fission.

CONCLUSION YQHX improves cardiac structure and function after MI, potentially by promoting myocardial mitochondrial midzone fission and inhibiting mitochondrial peripheral fission in ischemic cardiomyocytes.