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骨髓间充质干细胞分泌的外泌体携带的MicroRNA-214-3p通过靶向CD151影响阿尔茨海默病大鼠的氧化应激。

MicroRNA-214-3p Delivered by Bone Marrow Mesenchymal Stem Cells-Secreted Exosomes Affects Oxidative Stress in Alzheimer's Disease Rats by Targeting CD151.

作者信息

Zhang Luzy

机构信息

School of Pharmacy and Food Science, Zhuhai College of Science and Technology (Zhuhai College of Jilin University), Zhuhai, Guangdong, China.

出版信息

Organogenesis. 2025 Dec;21(1):2489673. doi: 10.1080/15476278.2025.2489673. Epub 2025 Apr 27.

Abstract

OBJECTIVE

This study probed the effect of targeted regulation of CD151 by microRNA-214-3p (miR-214-3p) delivered by bone marrow mesenchymal stem cells-secreted exosomes (BMSCs-exo) on oxidative stress and apoptosis of neurons in Alzheimer's disease (AD).

METHODS

Rat BMSCs were isolated, from which MSCs-exo were extracted and identified. The AD rat model was established and injected with MSC-exo suspension. Meanwhile, miR-214-3p and CD151 interfering lentivirus were transfected in MSCs. After injection, learning and cognitive ability of the rats were assessed, as well as neuronal apoptosis and oxidative stress injury. miR-214-3p and CD151 levels were determined, and their relationship was explored.

RESULTS

AD rats had prolonged escape latency, weakened learning and cognitive ability, increased neuronal apoptosis in the hippocampal CA3 region, and aggravated oxidative stress. After MSC-exo injection, these changes in AD rats were partially rescued. CD151 was targeted by miR-214-3p, and MSC-exo improved AD in rats through the miR-214-3p/CD151 axis.

CONCLUSION

MSC-exo down-regulates CD151 by targeting miR-214-3p to enhance antioxidant capacity, thereby improving the pathological injury of AD rats.

摘要

目的

本研究探讨骨髓间充质干细胞分泌的外泌体(BMSCs-exo)递送的微小RNA-214-3p(miR-214-3p)对阿尔茨海默病(AD)神经元氧化应激和凋亡的靶向调控作用。

方法

分离大鼠骨髓间充质干细胞,提取并鉴定间充质干细胞外泌体。建立AD大鼠模型并注射间充质干细胞外泌体悬液。同时,在间充质干细胞中转染miR-214-3p和CD151干扰慢病毒。注射后,评估大鼠的学习和认知能力,以及神经元凋亡和氧化应激损伤。测定miR-214-3p和CD151水平,并探讨它们之间的关系。

结果

AD大鼠逃避潜伏期延长,学习和认知能力减弱,海马CA3区神经元凋亡增加,氧化应激加重。注射间充质干细胞外泌体后,AD大鼠的这些变化得到部分缓解。CD151是miR-214-3p的靶点,间充质干细胞外泌体通过miR-214-3p/CD151轴改善大鼠AD症状。

结论

间充质干细胞外泌体通过靶向miR-214-3p下调CD151,增强抗氧化能力,从而改善AD大鼠的病理损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69af/12036478/90c756451b48/KOGG_A_2489673_F0001_OC.jpg

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