Abstract:

Objective To evaluate the cardioprotective effects and underlying mechanisms of neurotrophin-3 modified messenger RNA （NTF3 modRNA） following myocardial infarction （MI）， and to provide experimental and theoretical evidence for modRNA-based cardiac regeneration therapy. Methods In vitro， NTF3 modRNA was transfected into H9C2  cardiomyocytes. The transfection efficiency and NTF3 protein expression were examined by ELISA analysis， while flow cytometry was used to assess the anti-apoptotic effects. In vivo， a rat model of myocardial infarction was established， and NTF3 modRNA was injected intramyocardially into the infarct border zone. Cardiac function was evaluated by echocardiography after treatment， and cardiac electrophysiological recordings were used to evaluate the restoration of electrical conduction. Myocardial fibrosis and apoptosis were examined using Masson’s trichrome staining and TUNEL assay， respectively. Immunofluorescence for angiogenic markers （CD31 and α-SMA） was performed to assess neovascularization. Results NTF3 modRNA achieved efficient transfection and significantly increased NTF3 protein expression in H9C2 cells， leading to a marked reduction in apoptosis. In the rat MI model， intramyocardial delivery of NTF3 modRNA significantly improved left ventricular ejection fraction （LVEF） and fractional shortening （FS）， reduced myocardial fibrosis and decreased the number of TUNEL-positive cardiomyocytes. Electrical conduction recovery was markedly enhanced compared with the control group. Moreover， the expression of angiogenic markers was notably elevated. These findings suggest that NTF3 modRNA promotes myocardial repair and functional recovery by enhancing angiogenesis and cardiomyocyte survival. Conclusion NTF3 modRNA effectively mitigates post-infarction cardiac dysfunction by promoting angiogenesis， inhibiting cardiomyocyte apoptosis， and improving electrical conduction， thereby exerting significant cardioprotective and regenerative effects. This study provides new experimental insights and a potential therapeutic strategy for modRNA-based cardiac repair.

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