南京医科大学高隽小组的一项最新研究探明了靶向MiR-137的细胞外囊泡增强的治疗效果通过减轻缺血性卒中后神经元损伤有助于功能恢复。这一研究成果发表在2025年6月23日出版的国际学术期刊《神经科学通报》上。

课题组人员评估了脑缺血和再灌注（I/R）后miR-137的调控，并开发了一种细胞外囊泡（EV）靶向递送疗法。结果显示，I/R后小鼠海马区miR-137表达增强。miR-137通过降低Sirtuin1 （Sirt1）的表达调控缺血诱导的细胞死亡。因此，研究人员评估了一种涉及间充质干细胞衍生的EV的治疗方法。通过狂犬病病毒和糖蛋白修饰的EV系统递送anti-miR-137，可以特异性靶向神经元。anti-miR-137处理后，缺血小鼠存活率提高，部分神经行为缺陷得到缓解。该研究团队还证实，Maged1缺失可减轻缺血损伤并抑制miR-137的富集。

此外，miR-137的升高通过MAGED1/miR-137/Sirt1通路增加I/R后神经元死亡和神经功能缺损。结合狂犬病病毒、糖蛋白修饰EV和anti-miR-137，这是一种靶向miR-137调控缺血性神经元损伤和功能恢复的新策略。

据介绍，缺血性中风是导致死亡的主要原因，尤其是在老年人群中。已知MicroRNA-137 （miR-137）参与神经发育。然而，其在缺血性脑卒中中的作用尚不清楚。

附：英文原文

Title: Enhanced Therapeutic Effects of Extracellular Vesicles Targeting MiR-137 Contribute to Functional Recovery by Attenuating Neuronal Injury After Ischemic Stroke

Author: Zhang, Hui-Xin, Tao, Li-Qing, Chen, Yi-Hang, Jiang, Tian-Yi, Ye, Zhi-Yuan, She, Wen, Chen, Chang-Ying, Han, Ya-Li, Qi, Cui, Shen, Chong, Gao, Jun

Issue&Volume: 2025-06-23

Abstract: Ischemic stroke is a leading cause of death, especially among aging populations. MicroRNA-137 (miR-137) is known to be involved in neurodevelopment. However, its role in ischemic stroke is still unexplored. Here, we assessed the regulation of miR-137 after cerebral ischemia and reperfusion (I/R) and developed a targeted delivery therapy by extracellular vesicles (EVs). Our results showed that miR-137 was enhanced in the hippocampus of mice after I/R. miR-137 regulated the ischemia-induced cell death by decreasing the expression of Sirtuin1 (Sirt1). Therefore, we evaluated a therapeutic approach involving mesenchymal stem cell-derived EVs. Systemic delivery of anti-miR-137 by rabies virus glycoprotein-modified EVs allowed specific targeting of neurons. After anti-miR-137 treatment, the survival rate was increased in ischemic mice, and some neurobehavioral deficits were alleviated. We also established that Maged1 deficiency attenuated ischemic damage and inhibited miR-137 enrichment. Besides, the increase of miR-137 increased neuronal death and neurological deficits after I/R through the MAGED1/miR-137/Sirt1 pathway. Combined with rabies virus glycoprotein-modified EVs and anti-miR-137, this is a new strategy for regulating ischemic neuronal injury and functional recovery by targeting miR-137.

DOI: 10.1007/s12264-025-01437-w

Source: https://link.springer.com/article/10.1007/s12264-025-01437-w