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推拿对神经病理性疼痛大鼠内侧前额叶皮质突触可塑性的影响OA

Effects of Massage on Synaptic Plasticity in Medial Prefrontal Cortex of Rats with Neuropathic Pain

中文摘要英文摘要

目的 观察推拿对神经病理性疼痛大鼠内侧前额叶皮质(mPFC)突触可塑性的影响,探讨其发挥中枢镇痛作用的机制.方法 36只SD大鼠随机分成空白组、模型组和推拿组,每组12只.制备坐骨神经慢性压迫损伤模型模拟神经病理性疼痛,造模后第4日起对推拿组予推拿干预(5 N,120次/min,10 min/次,1次/d),连续14 d.分别于造模前及造模后第4、10、14、17日测定大鼠患侧后肢机械缩足阈值(PWT)和热缩足潜伏期(PWL),干预结束后,取左侧mPFC组织,采用透射电镜观察突触超微结构,免疫组化染色检测N-甲基-D-天冬氨酸受体(NR)2B蛋白定位及表达,Western blot检测mPFC突触功能关键蛋白NR2B、钙调蛋白依赖性蛋白激酶(CaMK)Ⅱ、突触后致密物(PSD)-95、突触素(SYP)蛋白表达.结果 与空白组比较,模型组大鼠PWT和PWL显著降低(P<0.001),mPFC神经元突触数量减少、突触间隙增宽、PSD变薄、突触活性带缩短、突触界面曲率降低(P<0.05),mPFC组织NR2B阳性表达显著升高(P<0.001),NR2B、CaMKⅡ蛋白表达显著升高(P<0.001),PSD-95、SYP蛋白表达显著降低(P<0.001);与模型组比较,推拿组大鼠PWT和PWL显著升高(P<0.001),mPFC神经元突触数量增多、突触间隙变窄、PSD增厚、突触活性带延长、突触界面曲率升高(P<0.05),mPFC组织NR2B阳性表达显著降低(P<0.01),NR2B、CaMKⅡ蛋白表达显著降低(P<0.05),PSD-95、SYP蛋白表达显著升高(P<0.05).结论 推拿能有效缓解坐骨神经慢性压迫损伤模型大鼠神经病理性疼痛,其潜在中枢镇痛机制可能与下调mPFC脑区过度激活的NR2B/CaMKⅡ信号通路,抑制神经元异常兴奋,同时上调PSD-95与SYP表达,促进突触结构重塑与功能优化,从而改善mPFC神经网络整体功能,恢复其对下行疼痛通路的调控有关.

Objective To observe the effects of massage on synaptic plasticity of medial prefrontal cortex(mPFC)in rats with neuropathic pain;To explore its mechanism of central analgesia.Methods Totally 36 SD rats were randomly divided into blank group,model group and massage group(n=12).A chronic compression injury of sciatic nerve model was established to simulate neuropathic pain.Starting from the 4th day after modeling,the massage group received massage intervention(5 N,120 times/min,10 min/day)for 14 consecutive days,while the blank group and model group received no intervention.The mechanical paw withdrawal threshold(PWT)and thermal paw withdrawal latency(PWL)of affected hind limb were measured before modeling and on days 4,10,14,and 17 after modeling.After the intervention,the left mPFC tissue was collected,synaptic structures were observed by transmission electron microscopy,the location and expression of NMDA receptor(NR)2B were analyzed by immunohistochemistry,the protein expression of NR2B,calcium/calmodulin-dependent protein kinase(CaMK)Ⅱ,postsynaptic density protein(PSD)-95 and synapsin(SYP)in mPFC were detected by Western blot.Results Compared with the blank group,PWT and PWL in the model group rats significantly decreased(P<0.001),the number of synapses in mPFC neurons decreased,the synaptic space widened,the PSD became thinner,the synaptic active band shortened,and the curvature of synaptic interface decreased(P<0.05),the positive expression of NR2B in mPFC tissue increased significantly(P<0.001),the protein expressions of NR2B and CaMKⅡ increased significantly(P<0.001),and the protein expressions of PSD-95 and SYP decreased significantly(P<0.001).Compared with the model group,PWT and PWL in the massage group significantly increased(P<0.001),the number of synapses in mPFC neurons increased,the synaptic space narrowed,the PSD thickened,the synaptic active band elongated,and the curvature of synaptic interface increased(P<0.05),the positive expression of NR2B in mPFC significantly decreased(P<0.01),the protein expressions of NR2B and CaMKⅡ significantly decreased(P<0.05),and the protein expressions of PSD-95 and SYP significantly increased(P<0.05).Conclusion Massage can effectively relieve neuropathic pain in rats with chronic compression injury of sciatic nerve.The underlying central analgesic mechanism may involve the bidirectional regulation of synaptic protein expression in mPFC,namely by down-regulating the overactivated NR2B/CaMKⅡsignaling pathway to inhibit neuronal hyperexcitability,and up-regulating PSD-95 and SYP to promote synaptic reconstruction and functional optimization,thereby restoring the mPFC management of descending pain pathways.

何露滢;陈祖璋;黄红叶;黄丽梅;林志刚;陈乐春;陈水金

福建中医药大学,福建 福州 350122福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003福建中医药大学附属康复医院,福建 福州 350003||福建省康复技术重点实验室,福建 福州 350003

医药卫生

神经病理性疼痛推拿内侧前额叶皮质突触可塑性N-甲基-D天冬氨酸受体大鼠

neuropathic painmassagemedial prefrontal cortexsynaptic plasticityNR2Brats

《中国中医药信息杂志》 2026 (4)

65-71,7

国家自然科学基金青年科学基金(82505785)福建省自然科学基金面上项目(2024J01141)福建省卫生健康中青年领军人才研修培养项目(2024年)

10.19879/j.cnki.1005-5304.202509660

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