Astragaloside IV Alleviates Myocardial Fibrosis After Myocardial Infarction through SIRT3/β-catenin/PPARγ Signaling Pathway

Background Myocardial fibrosis following myocardial infarction (MI) is linked to decreased cardiac function and heart failure. Astragaloside IV (AST IV), a component of traditional Chinese medicine, has shown promise in animal studies for improving cardiac function. Objectives This study intends to investigate the role of AST IV in MI and its correlation with the sirtuin-3 (SIRT3)/β-catenin/peroxisome proliferator-activated receptor gamma (PPARγ) signaling pathway. Materials and Methods After the establishment of an animal model of MI, 60 rats were divided into a control group, model group (MI group), positive control group (sham group), low-dose AST IV group (0.8 mg/100 g), and high-dose AST IV group (3 mg/100 g). The animals were injected once a day for 4 consecutive weeks. To further investigate the mechanism of action of AST IV, another nine rats from the model group were randomly divided into the 3TYP group (5 mg/100 g), SKL2001 group (20 µmol/L, 10 mL/kg), and T0070907 group (0.15 mg/100 g), with three rats in each group. The rats in each group were intervened once a day by intraperitoneal injection and once a day by gavage for 4 consecutive weeks. Hemodynamics, cardiac function, ventricular weight, and infarct area were assessed at 1, 2, and 4 weeks post-surgery. Myocardial collagen content in the non-infarcted area was measured, the expression rate of transforming growth factor-beta and ED-positive cells was calculated, and reverse transcription polymerase chain reaction was used to detect SIRT3, β-catenin, and PPARγ mRNA expression. Results The left ventricular ejection fraction, short-axis shortening rate, and left ventricular mass in the model group were decreased obviously. AST IV treatment decreased systolic blood pressure, +dp/dtmax, –dp/dtmax, and left ventricular end-diastolic pressure, as well as reduced myocardial collagen deposition in rat hearts ( p < 0.05). AST IV inhibited the SIRT3/β-catenin/PPARγ signaling pathway when alleviating myocardial fibrosis. Intervention with SIRT3 blocker 3-TYP, β-catenin agonist SKL2001, and PPARγ blocker T0070907 reversed the inhibitory effect of AST IV on the signaling pathway. Conclusion AST IV exhibits significant anti-fibrotic effects, effectively reducing collagen deposition in the MI model, improving cardiac function parameters, and decreasing markers such as creatine kinase-MB. It significantly regulates SIRT3, β-catenin, and PPARγ to exert cardioprotective effects. The key mechanism involves inhibiting the SIRT3/β-catenin/PPARγ, offering an innovative strategy for post-MI treatment.