基于p38MAPK信号通路探讨推拿参与腰椎间盘突出症大鼠中枢镇痛的作用机制  

Discussion on the mechanism of Tuina participating in central analgesia in rats with lumbar disc herniation based on p38MAPK signal pathway

作　　者：姚重界 汤程 黄瑞信 方思瞳 房敏 朱清广[1,3] 孔令军[2,3] 程艳彬[1,3] YAO Chongjie;TANG Cheng;HUANG Ruixin;FANG Sitong;FANG Min;ZHU Qingguang;KONG Lingjun;CHENG Yanbin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200437,China;Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Tuina Research Institute,Shanghai Academy of Traditional Chinese Medicine,Shanghai 200437,China)

机构地区：[1]上海中医药大学附属岳阳中西医结合医院,上海200437 [2]上海中医药大学附属曙光医院,上海201203 [3]上海市中医药研究院推拿研究所,上海200437

出　　处：《中华中医药杂志》2023年第7期3348-3352,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.82030121,No.82004493);国家中医药管理局中医药创新团队及人才支持计划项目(No.ZYYCXTD-C-202008);上海市“超级博士后”资助项目(No.2022515);上海市“科技创新行动计划”启明星项目扬帆专项(No.23YF1447600)。

摘　　要：目的:探讨推拿通过p38丝裂原活化蛋白激酶(MAPK)信号通路抑制脊髓背角中枢敏化从而参与腰椎间盘突出症(L D H)大鼠镇痛的作用机制。方法:将32只大鼠随机分为假手术组、模型组、推拿组、推拿+p38激动剂组,采用背根神经节持续压迫(CCD)模型模拟LDH病理变化。推拿组大鼠在造模后第4天开始推拿干预术侧委中穴,推拿+p38激动剂组在此基础上鞘内注射Anisomycin。实验过程中,采用电子Von Frey对大鼠右后足缩足阈值(P W T)测试以观察机械痛阈值变化;干预结束后取大鼠L4-L6段脊髓背角组织,采用Western Bolt检测p38MAPK、p-p38MAPK以及炎症因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β蛋白表达水平。结果:模型组P W T造模后下降趋势明显,且均显著低于同期假手术组(P<0.01);推拿组P W T在造模后先降低后上升,并在第10至21天均显著高于同期模型组(P<0.01);推拿+p38激动剂组P W T在造模后先降低后保持稳定,但均显著低于同期推拿组(P<0.01)。Western Blot结果显示,与假手术组比较,模型组大鼠脊髓背角中p38MAPK、p-p38MAPK、TNF-α、IL-1β蛋白表达均显著升高(P<0.01);与模型组比较,推拿干预后的大鼠p38MAPK、p-p38MAPK、TNF-α、IL-1β蛋白表达均显著降低(P<0.01,P<0.05);与单纯推拿比较,推拿+p38激动剂组大鼠p38MAPK、p-p38MAPK、TNF-α、IL-1β蛋白表达均显著升高(P<0.01)。结论:推拿可能通过p38MAPK信号通路调控下游炎症反应,进而抑制脊髓背角中枢敏化从而参与LDH的镇痛环节。Objective:To discuss the mechanism of Tuina inhibiting central sensitization of spinal dorsal horn via p38 mitogen-activated protein kinase(MAPK)signal pathway to participate in analgesia in rats with lumbar disc herniation(LDH).Methods:Thirty-two rats were randomly divided into sham group,model group,Tuina group and Tuina+p38 agonist group.The pathological changes of LDH were simulated by chronic compression of dorsal root ganglion(CCD)model.Tuina intervention was implemented at the Weizhong(BL 40)point of the operation side from the 4th day after surgery in the Tuina group,and the Tuina+p38 agonist group was injected with Anisomycin intrathecally on this basis.During the experiment,the electronic Von Frey was used to test paw withdrawal threshold(PWT)of rats to observe the changes of mechanical pain threshold of rats.After the intervention,the L4-L6 spinal dorsal horn of rats was taken,the changes of p38MAPK,p-p38MAPK and inflammatory factor TNF-α,IL-1βwere detected by Western Bolt.Results:The mechanical pain threshold of the model group decreased significantly after modeling,and were significantly lower than that of the sham group at the same time point(P<0.01).The mechanical pain threshold of rats in the Tuina group decreased first and then increased after modeling,and was significantly higher than that of the model group at the same time point on the 10th to 21st days(P<0.01).The mechanical pain threshold of rats in the Tuina+p38 agonist group decreased first and then remained stable after modeling,but they were significantly lower than those in the Tuina group at the same time point(P<0.01).Western Blot showed that the protein expressions of p38MAPK,p-p38MAPK,TNF-αand IL-1βin the spinal dorsal horn of the model group were significantly higher than those in the sham group(P<0.01);compared with the model group,the protien expressions of p38MAPK,p-p38MAPK,TNF-αand IL-1βof rats after Tuina intervention were significantly decreased(P<0.01,P<0.05).Compared with simple Tuina,the protien expressions of p38MAP

关 键 词：推拿 腰椎间盘突出症 P38MAPK信号通路 神经病理性疼痛 镇痛 

分 类 号：R244.1[医药卫生—针灸推拿学]