Antiapoptotic Effect of Target Protein for Xklp2 on Diabetic Rat Cardiomyocytes

Abstract

This study investigates the potential of TPX2 in mitigating diabetic cardiomyopathy by modulating the Akt/FoxO1 signaling pathway. Diabetic cardiomyopathy was induced in rats using streptozotocin, and heart structure and function were assessed through echocardiography and HE staining. TPX2 expression in myocardial tissue was measured using qRT-PCR. Lentivirus was used to overexpress TPX2 specifically in myocardial tissue, followed by reassessment of cardiac structure and function. Immunohistochemical staining was employed to evaluate Caspase3 expression. In the diabetic cardiomyopathy group, rat hearts exhibited evident damage in structure and function, with increased Caspase3 expression in myocardial tissue. Conversely, TPX2 overexpression effectively improved heart structure and function while inhibiting Caspase3 upregulation. In H9C2 cells cultured with high glucose, TPX2 overexpression counteracted reduced cell activity and increased apoptosis rates. It also downregulated the mRNA levels of apoptosis-related factors (Bax, Caspase3, Caspase9) and promoted anti-apoptotic factor Bcl-2 mRNA. TPX2 overexpression inhibited Caspase3 and Caspase9 activities, upregulated Akt mRNA and protein expression, and inhibited FoxO1 mRNA and protein expression. This suggests that TPX2 may regulate the Akt/FoxO1 signaling pathway, reducing apoptosis and cardiomyocyte toxicity induced by high glucose. These findings offer potential drug targets and therapeutic strategies for diabetic cardiomyopathy treatment.