解放军医学杂志2025，Vol.50Issue(2)：207-213,7.DOI:10.11855/j.issn.0577-7402.1084.2024.1118
hUC-MSCs-Exos不同给药方式对缺氧缺血性脑损伤新生小鼠的神经保护作用
Comparison of neuroprotective effects of hUC-MSCs-Exos on hypoxic-ischemic brain injury in neonatal mice by different administration modes
摘要
Abstract
Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.关键词
缺氧缺血性脑损伤/人脐血间充质干细胞来源外泌体/神经保护/鼻内注射Key words
hypoxic ischemic brain damage/exosomes of human umbilical cord mesenchymal stem cells/neuroprotection/nasal injection分类
临床医学引用本文复制引用
胡筱霞,赛依帕,陈星星,崔维静,王三萍,罗璇,吴世丽..hUC-MSCs-Exos不同给药方式对缺氧缺血性脑损伤新生小鼠的神经保护作用[J].解放军医学杂志,2025,50(2):207-213,7.基金项目
This work was supported by the Natural Science Foundation of Gansu Province(22JR5RA689),the Gansu Youth Science and Technology Fund Project(22JR5RA701),the Key Laboratory of Molecular Diagnosis and Precision Therapy of Surgical Tumor of Gansu Province(GSSZDSYS2020-10),and the Research Foundation of People's Hospital of Gansu Province(20GSSY1-13) 甘肃省自然科学基金(22JR5RA689) （22JR5RA689）
甘肃省青年科技基金计划项目(22JR5RA701) （22JR5RA701）
甘肃省外科肿瘤分子诊断与精准治疗重点实验室项目(GSSZDSYS2020-10) （GSSZDSYS2020-10）
甘肃省人民医院院内科研基金(20GSSY1-13) （20GSSY1-13）
