Abstract
Objective: This study aims to investigate the mechanism of AGS-IV in treating diabetic cardiomyopathy (DCM) by establishing animal and cellular models of the disease. Methods: A DCM rat model was established by feeding a high-fat diet combined with streptozotocin (STZ) injection, and a DCM cell model was created through glucose induction. In model rats, the cardiac weight-to-body weight ratio, the left ventricular weight-to-heart weight ratio, and ventricular wall thickness were measured. ELISA was used to detect Collagen1 and MMP-2 levels in myocardial tissue, serum, and cultured cells. The mRNA levels of GNG2, MRAS, and ERK in myocardial tissue and cultured cells were measured using RT-PCR. Results: In vivo, experiments demonstrated that AGS-IV effectively reduced the cardiac weight-to-body weight ratio, left ventricular weight-to-heart weight ratio, and ventricular wall thickness in DCM rat models. It also decreased Collagen I levels in myocardial tissue and MMP-2 levels in serum, accompanied by downregulated mRNA expression of GNG2, MRAS, and ERK in myocardial tissue. In vitro, AGS-IV significantly reduced Collagen I and MMP-2 levels in DCM cell models and downregulated GNG2, MRAS, and ERK mRNA expression. Conclusion: AGS-IV exerts therapeutic effects on DCM by regulating the GNG2/MRAS-ERK signaling pathway.