新医学2026，Vol.57Issue(6)：601-611,11.DOI:10.12464/j.issn.0253-9802.2026-0490
黑色素纳米颗粒促线粒体转移增强干细胞神经保护
Melanin nanoparticles enhance stem cell-mediated neuroprotection by promoting mitochondrial transfer
摘要
Abstract
Objective To investigate the regulatory effect of melanin nanoparticle(MNP)pretreatment on mitochondrial transfer from bone marrow mesenchymal stem cells(BMSCs),as well as its protective effect and potential mechanisms in enhancing BMSC-mediated protection of neurons injured by ischemia and hypoxia.Methods Primary cortical neurons were treated with oxygen-glucose deprivation(OGD)to establish an in vitro ischemic injury model.The neurons were randomly divided into seven groups:the Normal control group,OGD group,OGD+MNPs group,OGD+BMSCs group,OGD+MNPs-BMSCs group,Transwell+BMSCs group,and Transwell+MNPs-BMSCs group.MitoTracker Green/Red dual-label tracing combined with laser confocal microscopy and flow cytometry was used to quantitatively analyze the efficiency of intercellular mitochondrial transfer.Neuronal cell viability,reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and levels of the key metabolites of the pentose phosphate pathway,reduced nicotinamide adenine dinucleotide phosphate(NADPH)and reduced glutathione(GSH),were measured in each group.Western blotting was used to detect changes in the expression of translocase of outer mitochondrial membrane 20(TOMM20),mitofusin 2(MFN2),and dynamin-related protein 1(DRP1).Results Compared with the OGD+BMSCs group,the OGD+MNPs-BMSCs group showed increased neuronal viability(P＜0.000 1).MNP pretreatment increased the efficiency of mitochondrial transfer from BMSCs to neurons by 1.6-fold(P＜0.05),and this process depended on direct intercellular contact,as the transfer efficiency decreased after physical separation by Transwell(P＜0.05).Mechanistically,compared with the OGD group,neurons in the OGD+MNPs-BMSCs group showed decreased ROS and MDA levels and increased SOD activity(all P＜0.05).Metabolic activity of the pentose phosphate pathway was enhanced,and NADPH and GSH levels were increased(both P＜0.05).The expression levels of the mitochondrial dynamics-related proteins TOMM20 and MFN2 were upregulated,while DRP1 expression was downregulated(all P＜0.05).Conclusions MNPs can promote functional mitochondrial transfer from BMSCs to neurons injured by ischemia and hypoxia,thereby enhancing endogenous antioxidant capacity in neurons,activating metabolic homeostasis of the pentose phosphate pathway,and improving mitochondrial fusion-fission imbalance and biogenesis impairment,ultimately exerting a synergistic neuroprotective effect.关键词
缺血性卒中/黑色素纳米颗粒/骨髓间充质干细胞/线粒体转移/线粒体动力学/能量代谢Key words
Ischemic stroke/Melanin nanoparticles/Bone marrow mesenchymal stem cells/Mitochondrial transfer/Mitochondrial dynamics/Energy metabolism引用本文复制引用
潘文雯,李蔓,孔德燕..黑色素纳米颗粒促线粒体转移增强干细胞神经保护[J].新医学,2026,57(6):601-611,11.基金项目
广西自然科学基金(2025GXNSFAA069341) （2025GXNSFAA069341）
广西自然科学基金区域高发疾病研究联合专项(2023GXNSFAA026197) （2023GXNSFAA026197）
