组织工程与重建外科杂志2025，Vol.21Issue(6)：543-554,12.DOI:10.3969/j.issn.1673-0364.2025.06.005
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
Preliminary study on NTF3 modRNA in the treatment of myocardial infarction by promoting angiogenesis and inhibiting cell apoptosis
摘要
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.关键词
神经营养素-3/神经营养素-3修饰信使核糖核酸/心肌梗死/心脏再生Key words
Neurotrophin-3/NTF3 modRNA/Myocardial infarction/Cardiac regeneration分类
医药卫生引用本文复制引用
唐欣,王伟,付炜,卢婷婷,王会景,于新迪,丁雷,刘明璐,李凯祥,林鑫俊,黄佳楚..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[J].组织工程与重建外科杂志,2025,21(6):543-554,12.基金项目
国家自然科学基金面上项目(82272178),上海儿童医学中心海南医院金椰种子基金(2024JYZZ-FY-05),2024年三亚科技繁星专项(2024KJFX054),金椰种子-妇儿分子医学重点实验室开放基金项目(2025JYZZ-ZDSYS-01),上海市东方英才计划拔尖项目(BJKJ2024012),安徽省感染与免疫安徽省重点实验室开放课题(AHIAI2023K01),胚胎干细胞研究湖北省重点实验室(湖北医药学院)开放课题(2025ESOF006). （82272178）
