Exosomal miR-23b from bone marrow mesenchymal stem cells alleviates oxidative stress and pyroptosis after intracerebral hemorrhage

作     者：Liu-Ting Hu Bing-Yang Wang Yu-Hua Fan Zhi-Yi He Wen-Xu Zheng Liu-Ting Hu;Bing-Yang Wang;Yu-Hua Fan;Zhi-Yi He;Wen-Xu Zheng

作者机构：Department of NeurologyThe First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong ProvinceChina Department of NeurologyThe First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina Geriatric Department of Dalian Friendship HospitalDalianLiaoning ProvinceChina 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2023年第18卷第3期

页      面：560-567页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100204[医学-神经病学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China No.81571120(to ZYH). 

主　　题：bone marrow mesenchymal stem cells exosomal miRNAs intracerebral hemorrhage miR-23b neuroinflammation NLRP3 inflammasome Nrf2 oxidative stress PTEN pyroptosis 

摘      要：Our previous studies showed that miR-23b was downregulated in patients with intracerebral hemorrhage(ICH). This indicates that miR-23b may be closely related to the patho-physiological mechanism of ICH, but this hypothesis lacks direct evidence. In this study, we established rat models of ICH by injecting collagenase Ⅶ into the right basal ganglia and treating them with an injection of bone marrow mesenchymal stem cell(BMSC)-derived exosomal miR-23b via the tail vein. We found that edema in the rat brain was markedly reduced and rat behaviors were improved after BMSC exosomal miR-23b injection compared with those in the ICH groups. Additionally, exosomal miR-23b was transported to the microglia/macrophages, thereby reducing oxidative stress and pyroptosis after ICH. We also used hemin to mimic ICH conditions in vitro. We found that phosphatase and tensin homolog deleted on chromosome 10(PTEN) was the downstream target gene of miR-23b, and exosomal miR-23b exhibited antioxidant effects by regulating the PTEN/Nrf2 pathway. Moreover, miR-23b reduced PTEN binding to NOD-like receptor family pyrin domain containing 3(NLRP3) and NLRP3 inflammasome activation, thereby decreasing the NLRP3-dependent pyroptosis level. These findings suggest that BMSC-derived exosomal miR-23b exhibits antioxidant effects through inhibiting PTEN and alleviating NLRP3 inflammasome-mediated pyroptosis, thereby promoting neurologic function recovery in rats with ICH.