Spermine: A prospective treatment for high glucose-induced myocardial fibrosis in db/db mice

Document Type : Original Article

Authors

1 Animal Research Institute, Research Department, Mudanjiang Medical University, Mudanjiang, China

2 School of Basic Medical Sciences, Mudanjiang Medical University, Mudanjiang, China

3 Department of Immunology, Mudanjiang Medical University, Heilongjiang, China

4 Mudanjiang Traditional Chinese Medicine Hospital, Mudanjiang, China

5 School of Stomatology, Mudanjiang Medical University, Mudanjiang, China

10.22038/ijbms.2025.83464.18060

Abstract

Objective(s): This study explored the molecular mechanism by which exogenous spermine attenuates diabetic cardiomyopathy (DCM)-induced myocardial fibrosis.
Materials and Methods: db/db mice and primary neonatal mouse cardiac fibroblasts were used to conduct in vivo and in vitro experiments. The levels of total cholesterol (TC), triglycerides (TG), creatine kinase isoenzyme (CK-MB), troponin I (cTnI), and lactate dehydrogenase (LDH) were measured. Heart function and collagen deposition were assessed using echocardiographic analysis, Masson staining, and Sirius red staining. Cell proliferation and migration were analyzed using EdU and transwell assays. Relevant protein expression was evaluated by immunohistochemistry and western blot.
Results: After 12 weeks, the mice in the type 2 diabetes (T2D) group exhibited increased blood glucose, TG, TC, and serum myocardial marker enzyme levels. Ejection fraction (EF) and left ventricular fractional shortening left ventricular fractional shortening (FS) decreased, while LVIDs and LVIDd increased. Significant collagen fiber deposition and increased HW/TL ratio, SSAT, α-SMA, TGF-β1, and Collagen-I/III expression was observed in myocardial tissue. Conversely, ODC expression was down-regulated. In the T2D + spermine (SP) group, these trends were reversed. In vitro, high glucose conditions led to increased proliferation of cardiac fibroblasts. SSAT, α-SMA, TGF-β1, Collagen-I/III, MMP-2, MMP-9, p-Smad-2, TβRI, and TβRII were up-regulated, while ornithine decarboxylase (ODC) expression was down-regulated. Interestingly, these changes were reversed in the HG + SP group.
Conclusion: Our findings demonstrate that SP reduces collagen synthesis and secretion by inhibiting the TGF-β1/Smads signaling pathway. These results provide new insights into potential therapeutic approaches for DCM.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 7
July 2025
Pages 907-915

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