基于SIRT1/BDNF/TrkB信号通路探讨推拿对神经病理性疼痛大鼠疼痛伴抑郁行为的影响  

Exploration on the Effects of Tuina on Pain and Depressive Behaviors in Neuropathic Pain Rats Based on SIRT1/BDNF/TrkB Signaling Pathway

作　　者：王晓华 林志刚 陈水金 陈乐春 蒋晶晶 张幻真 陈进城 黄红叶 WANG Xiaohua;LIN Zhigang;CHEN Shuijin;CHEN Lechun;JIANG Jingjing;ZHANG Huanzhen;CHEN Jincheng;HUANG Hongye(Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China;Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine,Fuzhou 350003,China;Fujian Key Laboratory of Rehabilitation Technology,Fuzhou 350003,China)

机构地区：[1]福建中医药大学,福建福州350122 [2]福建中医药大学附属康复医院,福建福州350003 [3]福建省康复技术重点实验室,福建福州350003

出　　处：《中国中医药信息杂志》2025年第3期89-97,共9页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金(82174523、82105039、82205303);福建省自然科学基金(2023J06037)。

摘　　要：目的探讨推拿对神经病理性疼痛(NP)大鼠疼痛伴抑郁行为的影响及其可能作用机制。方法102只SD大鼠随机分为空白组、假手术组、模型组、推拿组、抑制剂组和抑制剂+推拿组,每组17只。通过坐骨神经慢性压迫损伤方式建立NP模型,造模第8日起进行推拿干预和海马CA1区注射沉默信息调节因子1(SIRT1)抑制剂EX-527(20μg/μL,0.5μL),连续14 d。分别于术前1 d和术后第7、14、21日采用机械缩足反射检测大鼠疼痛行为,强迫游泳实验和糖水偏好实验检测抑郁行为;Nissl染色观察海马CA1区神经元形态和数量,高尔基染色观察海马CA1区神经元树突棘密度,免疫荧光染色、Western blot和RT-qPCR检测海马组织SIRT1/BDNF/TrkB信号通路相关蛋白及mRNA表达。结果与假手术组比较,模型组大鼠术后第7、14、21日机械缩足反射阈值显著降低(P<0.001),强迫游泳不动时间显著延长(P<0.001),糖水偏好率显著降低(P<0.001);海马CA1区神经元形态异常,Nissl阳性细胞数量显著减少(P<0.001),树突棘密度显著降低(P<0.001);海马齿状回SIRT1、BDNF、TrkB表达显著降低(P<0.01,P<0.001),SIRT1、BDNF、TrkB蛋白和mRNA表达显著降低(P<0.001)。与模型组比较,推拿组术后第14、21日机械缩足反射阈值显著升高(P<0.01、P<0.001),强迫游泳不动时间显著缩短(P<0.01,P<0.001),糖水偏好率显著升高(P<0.001);海马CA1区神经元形态明显改善,Nissl阳性细胞数量显著增加(P<0.001),树突棘密度显著升高(P<0.001);海马齿状回SIRT1、BDNF、TrkB表达显著升高(P<0.01,P<0.001),SIRT1、BDNF、TrkB蛋白和m RNA表达显著升高(P<0.001)。SIRT1抑制剂EX-527能明显抑制推拿产生的改善作用。结论推拿可能通过激活SIRT1/BDNF/TrkB信号通路改善海马神经元结构可塑性,从而有效缓解NP大鼠疼痛伴抑郁行为。Objective To investigate the effects and potential mechanism of tuina on pain and depressive behaviors in rats with neuropathic pain(NP).Methods A total of 102 SD rats were randomly divided into blank group,sham-operation group,model group,tuina group,inhibitor group and inhibitor+tuina group,with 17 rats in each group.The NP model was established by chronic constriction injury of the sciatic nerve.Starting from the 8th day post-operation,the rats underwent a 14-day tuina intervention and stereotactic injection of the SIRT1 inhibitor EX-527(20μg/μL,0.5μL)into the hippocampal CA1 region.Pain behaviors were assessed using the mechanical withdrawal threshold test one day before operation and on days 7,14 and 21 post-operation.Depressive behaviors were evaluated using the forced swimming test and sucrose preference test.Nissl staining was employed to observe neuronal morphology and quantity in the hippocampal tissue,while Golgi staining was used to examine dendritic spine density,hippocampal expression of SIRT1/BDNF/TrkB signaling pathway related protein and mRNA were analyzed using immunofluorescence,Western blot and RT-qPCR.Results Compared with the sham-operation group,the model group showed a significant decrease in mechanical withdrawal threshold(P<0.001),prolonged immobility time in the forced swimming test and reduced sucrose preference(P<0.001)on days 7,14 and 21 post-operation;the morphology of hippocampal CA1 neurons was abnormal,with a significant decrease in the number of Nissl positive cells(P<0.001)and a significant decrease in dendritic spine density(P<0.001);the expressions of SIRT1,BDNF and TrkB in dentate gyrus of the hippocampus were significantly reduced(P<0.01,P<0.001),and the protein and mRNA expressions of SIRT1,BDNF and TrkB were significantly reduced(P<0.001).Compared with the model group,the tuina group showed a significant increase in mechanical withdrawal threshold(P<0.01,P<0.001)on days 14 and 21 post-operation,shortened immobility time in the forced swimming test(P<0.01,P<0.001)and in

关 键 词：推拿 神经病理性疼痛 抑郁 海马 SIRT1/BDNF/TrkB信号通路 大鼠 

分 类 号：R244.1[医药卫生—针灸推拿学]