昆明医科大学学报2025，Vol.46Issue(7)：74-83,10.DOI:10.12259/j.issn.2095-610X.S20250709
骨髓间充质干细胞移植对脊髓损伤后神经病理性疼痛大鼠的影响以及对LPS诱导神经元细胞的作用
Effects of Bone Marrow Mesenchymal Stem Cell Transplantation on Neuropathic Pain in Rats with Spinal Cord Injury and Its Action on LPS-Induced Neuronal Cells
摘要
Abstract
Objective To investigate the effects of BMSCs treatment on neuropathic pain in rats with SCI and explore the underlying mechanism.Methods The rats were randomly divided into the following groups(n=15 per group):sham-operated(sham)group,spinal cord injury model(SCI)group,SCI+BMSCs group,and SCI+BMSCs+LY294002 group.An SCI model was established using Sprague-Dawley rats,followed by intraspinal administration of BMSCs and the PI3K inhibitor LY294002 to the injured spinal cord of SCI rats.The BBB score,pMWT,and pTWL values under thermal stimulation were measured.Hematoxylin-eosin staining was used to observe pathological changes in the injured spinal cord of rats.The effects of BMSCs transplantation on SCI rats were explored through hematoxylin-eosin staining,immunofluorescence staining,ELISA,and Western Blot experiments.RSCN were induced using LPS and co-cultured with BMSCs and their exosomes.The effects of BMSCs and their exosomes on RSCN were investigated through Annexin V-FITC/PI kit,ELISA,and Western Blot assays.Results The SCI model was considered successfully established when the following criteria were met on post-operative day 5:BBB locomotor score≤5,accompanied by a BBB score<10 on day 20,along with histopathological evidence of spinal cord tissue loosening,extensive vacuolation,and neuronal atrophy observed via HE staining.Compared with the sham group,the SCI group exhibited significantly lower BBB scores,pMWT,and pTWL values(P<0.001).Concurrently,increased immunofluorescence intensity of IBA1,elevated levels of pro-inflammatory cytokines,and pain-related factors were detected in the spinal cord(P<0.001).Furthermore,activation of the PI3K/AKT signaling pathway was significantly suppressed.BMSCs transplantation protected SCI rats by activating the PI3K/AKT pathway(P<0.001).BMSC-mediated spinal cord repair was attenuated by LY294002 administration.LPS-induced RSCNs showed increased apoptosis and pro-inflammatory cytokine release(P<0.001).Co-culture with MSCs or BMSCs-derived exosomes activated the PI3K/AKT signaling pathway,thereby reducing LPS-induced apoptosis and proinflammatory cytokine production(P<0.05).Conclusion BMSCs activate the PI3K/AKT signaling pathway in neurons through exosomes,suppressing the levels of TNF-α,SP,NE,and 5-HT,and promoting functional recovery in SCI rats.关键词
骨髓间充质干细胞/脊髓损伤/神经病理性疼痛/致痛因子Key words
Bone marrow mesenchymal stem cells/Spinal cord injury/Neuropathic pain/Nociceptive factors分类
医药卫生引用本文复制引用
张明慧,温江涛,辛小梅,张宝惠..骨髓间充质干细胞移植对脊髓损伤后神经病理性疼痛大鼠的影响以及对LPS诱导神经元细胞的作用[J].昆明医科大学学报,2025,46(7):74-83,10.基金项目
临汾市人民医院院级课题(T20210512154) （T20210512154）
