郑州大学学报（医学版）2026，Vol.61Issue(3)：48-53,6.DOI:10.13705/j.issn.1671-6825.2025.05.037
高表达miR-135a的骨髓间充质干细胞来源的外泌体对细菌性脑膜炎新生大鼠神经损伤及FOXO1表达的影响
Effect of BMSC-derived exosomes with high miR-135a on neural injury and FOXO1 expression of neonatal rats with bacterial meningitis
摘要
Abstract
Aim:To investigate the effect of bone marrow mesenchymal stem cell-derived exosomes with high miR-135a expression(BMSC Exo-miR-135a)on neural injury and FOXO1 expression of neonatal rats with bacterial meningitis(BM).Methods:Rat BMSC were isolated and transfected with miR-135 mimic or miR-NC using liposome 3000 for 48 hours,exo-somes were isolated by density gradient centrifugation to obtain BMSC Exo-miR-135a and Exo-miR-NC.Sixty neonatal rats were randomly divided into a control group,BM group,Exo-miR-NC group,and Exo-miR-135a group,with 15 rats in each group.The cerebellomedullary pool of the BM group,Exo-miR-NC group,and Exo-miR-135a group was injected with group B streptococcus(GBS),6 hours later,physiological saline,Exo-miR-NC,and Exo-miR-135a were injected into the lateral ventricles,respectively.24 hours after GBS injection,neurobehavioral assessments were performed using the Loeffler scoring system,cerebrospinal fluid was collected to determine GBS colony count and white blood cell(WBC)count,and the levels of TNF-α,IL-1β,and IL-6 were measured by ELISA(n=15).Blood-brain barrier permeability was evaluated using EB as-say(n=5),and pathological changes in brain tissue were assessed by HE,Nissl,and TUNEL staining(n=5).RT-qPCR was used to detect the expression levels of miR-135a and FOXO1 mRNA in brain tissue,and Western blot was employed to detect FOXO1 protein expression(n=5).Results:Compared with the control group,the BM group rats exhibited reduced Loeffler score;increased GBS colony count,WBC count,inflammatory cytokine levels in cerebrospinal fluid,increased EB leakage volume,brain water content;fewer Nissl bodies and decreased miR-135a expression in brain tissue;increased HE staining score,apoptosis rate,and FOXO1 expression in brain tissue(P＜0.05).Treatment with Exo-miR-NC and Exo-miR-135a reversed these changes compared with the BM group(P＜0.05),with Exo-miR-135a treatment demonstrating more significant effects(P＜0.05).Conclusion:BMSC-Exo-miR-135a may exert neuroprotective effects on neonatal BM rats by targeting FOXO1 to mitigate inflammation and apoptosis.关键词
骨髓间充质干细胞/外泌体/miR-135a/FOXO1/细菌性脑膜炎/神经损伤Key words
bone marrow mesenchymal stem cells/exosome/miR-135a/FOXO1/bacterial meningitis/neuronal damage分类
医药卫生引用本文复制引用
李月云,王艳蕊,付艳..高表达miR-135a的骨髓间充质干细胞来源的外泌体对细菌性脑膜炎新生大鼠神经损伤及FOXO1表达的影响[J].郑州大学学报（医学版）,2026,61(3):48-53,6.基金项目
河南省医学科技攻关计划联合共建项目(LHGJ20230892) （LHGJ20230892）
