骨髓间充质干细胞源性外泌体LncRNA-EPB41L4A-AS1靶向调控uL3介导的YAP/Hippo途径抑制心肌细胞铁死亡缓解心力衰竭的作用机制研究

脂质过氧化应激在心肌损伤发生发展中起着重要调控作用，研究发现其异常活化可诱导心肌细胞铁死亡影响心衰的疾病进展。前期研究发现间髓间充质干细胞（BMSCs）外泌体（Exosome）治疗可显著上调EPB41L4A-AS1在HF小鼠中的表达，降低缺氧诱导的心肌细胞损伤有效抑制氧化应激反应。生物信息学预测，EPB41L4A-AS1和uL3具有潜在的结合位点，而YAP / Hippo信号通路可能参与调节EPB41L4A-AS1影响心肌细胞铁死亡的发生机制。本课题拟通过评价BMSCs-Exo对心力衰竭的缓解作用，确定其是否存在潜在治疗价值，重点关注BMSCs-Exo介导EPB41L4A-AS1对心肌细胞铁死亡的影响，初步探讨YAP/Hippo通路参与调控的分子机制。本研究将为BMSCs-Exo治疗HF提供实验基础及理论依据，为BMSCs-Exo在临床的推广应用提供科学依据，具有重要的临床应用价值及意义。

Lipid peroxidative stress plays an important role in the occurrence and development of myocardial injury. Studies have found that its abnormal activation can induce ferroptosis in myocardial cells and affect the progress of heart failure. Previous study demonstrated that BMSCs-Exo can significantly promote the expression of EPB41L4A-AS1 in HF mice, reduce myocardial cell damage induced by hypoxia, and effectively inhibit oxidative stress. Bioinformatics analysis predicted that EPB41L4A-AS1 and uL3 have potential binding sites, and the YAP/Hippo signaling pathway may be involved in regulating the mechanism of EPB41L4A-AS1 affecting cardiomyocyte ferroptosis. This project intends to evaluate the mitigation effect of BMMSC-Exo on heart failure, determine whether it has potential therapeutic value, and focus on the impact of BMMSC-Exo-mediated EPB41L4A-AS1 on cardiomyocyte ferroptosis, and preliminarily explore the molecular mechanisms of YAP/HIPPO signaling pathway involved in the regulation process. This project will provide the experimental foundations and theoretical basises for the treatment of BMMSC-Exo in HF, and will provide a scientific basis for the widely used of BMMSC-Exo in clinic. It will has important clinical application value and significance.