中国医学科学院学报2025，Vol.47Issue(4)：509-518,10.DOI:10.3881/j.issn.1000-503X.16494
脊髓脆性X智力低下蛋白和β-连环蛋白参与神经病理性疼痛的机制
Functional Mechanisms of Spinal Cord Fragile X Mental Retardation Protein and β-Catenin Involved in Neuropathic Pain
摘要
Abstract
Objective To explore the functional mechanism of spinal cord fragile X mental retardation protein(FMRP)involved in neuropathic pain(NP)by using the sciatic nerve model of chronic compression injury(CCI).Methods First,to investigate the changes of spinal cord FMRP and β-catenin following the de-velopment of NP,this study compared the 50％mechanical withdrawal threshold(MWT)and thermal withdraw-al latency(TWL)in CCI rats,as well as changes of FMRP and β-catenin in the spinal dorsal horn post-surger-y,through random grouping.Immunofluorescence staining was performed on spinal cord tissue sections from CCI rats.Second,to further validate the alterations in pain behavior when the FMRP function was lost,we measured the 50％MWT,TWL,and FMRP and β-catenin in the spinal dorsal horn after FMRP knockdown in CCI rats.Finally,we measured the 50％MWT,TWL,and FMRP and β-catenin in the case of FMRP hyperfunction for validation.Results Compared with the baseline CCI group and the naive and sham groups after modeling,the CCI group after modeling showed decreases in 50％MWT and TWL(all P＜0.001).After modeling,com-pared with the naive group and the sham group,the CCI group presented up-regulated expression of FMRP(P=0.027,P=0.022)and β-catenin(P＜0.001,P=0.001)in the spinal dorsal horn.No co-localization of FMRP with astrocytes and microglia was observed in the spinal cord,while the co-localization with neurons was observed.Compared with the baseline,the CCI+FMRP knockdown group showed decreases in 50％MWT(P=0.015)and TWL(P=0.001)after modeling.After intrathecal injection of small interfering RNA(siRNA),the 50％MWT(P=0.020)and TWL(P=0.009)of the CCI+FMRP knockdown group were increased.Moreover,compared with the CCI group and the CCI+solvent group,the CCI+FMRP knockdown group showed increases in 50％MWT(both P＜0.001)and TWL(P=0.005,P=0.006).After intrathecal injection of siRNA,the expression levels of FMRP(P=0.012,P=0.007)and β-catenin(both P＜0.001)in the spinal dorsal horn of the CCI+FMRP knockdown group were lower than those of the CCI group and the CCI+solvent group.Compared with the baseline FMRP overexpression group and the naive and negative control groups after ad-eno-associated virus(AAV)injection,the FMRP overexpression group after AAV injection showed decreases in 50％MWT and TWL(all P＜0.001).After AAV injection,compared with the naive group and the negative control group,the FMRP overexpression group demonstrated up-regulated expression of FMRP(both P＜0.001)and β-catenin(P=0.006,P=0.008)in the spinal cord.Conclusions This study confirms that spi-nal cord FMRP and β-catenin are involved in NP induced by CCI.Spinal cord FMRP may be one of the potential therapeutic targets for NP.关键词
脆性X智力低下蛋白/β-连环蛋白/神经病理性疼痛/脊髓Key words
fragile X mental retardation protein/β-catenin/neuropathic pain/spinal cord分类
医药卫生引用本文复制引用
张龙,赵劲松,周丽,陈磊,冯智英..脊髓脆性X智力低下蛋白和β-连环蛋白参与神经病理性疼痛的机制[J].中国医学科学院学报,2025,47(4):509-518,10.基金项目
国家自然科学基金(82271239) （82271239）
