组织工程与重建外科杂志

组织工程与重建外科杂志 ›› 2025, Vol. 21 ›› Issue (6): 543-.

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NTF3 modRNA通过促进血管生成并抑制细胞凋亡治疗心肌梗死的初步研究

  

  • 出版日期:2025-12-25 发布日期:2025-12-30

Preliminary study on NTF3 modRNA in the treatment of myocardial infarction by promoting angiogenesis and inhibiting cell apoptosis

  • Online:2025-12-25 Published:2025-12-30

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摘要：

目的 评估神经营养素-3修饰信使RNA（NTF3 modRNA）在心肌梗死后的心肌保护作用及其潜在机制，为基
于 modRNA 的心脏再生治疗提供实验依据。方法 首先，在体外实验中将 NTF3 modRNA 转染至 H9C2 细胞，通过
ELISA检测 NTF3 modRNA体外转染效果和 NTF3蛋白表达水平，并采用流式分析评估其抗凋亡效果。随后，在体内实
验中建立大鼠心肌梗死模型，于梗死区心肌内注射 NTF3 modRNA。术后通过超声心动图评估心功能变化及电传导功
能恢复情况，Masson染色与 TUNEL染色观察心肌纤维化与细胞凋亡情况，组织免疫荧光检测血管生成标志物（CD31、
α-SMA）表达评估血管生成。结果 NTF3 modRNA在H9C2细胞中实现了高效转染并显著上调NTF3蛋白表达，显著减
少细胞凋亡比例。在大鼠心肌梗死模型中，NTF3 modRNA注射组的左心室射血分数（LVEF）及缩短分数（FS）显著高于
对照组，心肌纤维化面积显著减少，TUNEL阳性细胞数明显降低；同时，心肌组织中血管生成标志物表达明显上调，心
脏电传导恢复更为充分，表明 NTF3 modRNA 可能通过促进血管生成和心肌细胞存活促进心肌修复与功能恢复。结
论 NTF3 modRNA通过促进血管生成、抑制心肌细胞凋亡及改善心脏电传导功能，可有效缓解心肌梗死后的心功能损
伤，显示出较好的心脏保护与再生潜力。该研究为基于modRNA的心脏修复策略提供了新的思路。

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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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