CQ复方对癌侵袭镜像痛模型小鼠的镇痛作用及其中枢机制探讨  

Analgesic effect and central mechanisms of CQ prescription on cancer invasion induced mirror image pain in model mice

作　　者：姜宇懋[1] 孙丹丹[1] 王志国[1] 李涛[1] 赵小亮[1] 焦玥[1] 刘洋[1] 李玉娟[1] 欧阳竟锋 王丹巧[1] JIANG Yu-mao SUN Dan-dan WANG Zhi-guo LI Tao ZHAO Xiao-liang JIAO Yue LIU Yang LI Yu-juan OUYANG Jing-feng WANG Dan-qiao(Experimental Research Center, China Academy of Chinese Medical Sciences, Be（iing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment of Major Diseases, Beijing 100700, China)

机构地区：[1]中国中医科学院医学实验中心北京市中医药防治重大疾病基础研究重点实验室,北京100700

出　　处：《中国中药杂志》2017年第4期739-745,共7页China Journal of Chinese Materia Medica

基　　金：国家科技部国际科技合作专项(2010DFA31890);中国中医科学院自主选题研究项目(ZZ2013003)

摘　　要：该研究旨在了解CQ复方对癌侵袭镜像痛(cancer invasion induced mirror image pain,CIIMIP)模型小鼠的镇痛作用及其相关中枢机制。将雄性BALB/c小鼠随机分为正常组、操作对照组(注射0.2 m L灭活的S180肉瘤细胞液)、模型组(于右腿股骨大转子处注射0.2 m L S180肉瘤细胞液)、CQ复方低剂量组(模型+100 mg·kg^(-1),ip)、CQ复方中剂量组(模型+150 mg·kg^(-1),ip)、CQ复方高剂量组(模型+200 mg·kg^(-1),ip),造模前及术后用Von Frey纤维丝测定镜像侧后足的机械缩足阈值(mechanical withdrawal threshold,MWT);采用高效液相-荧光法(HPLC-FLD)检测脊髓L3~L5节段内谷氨酸(Glu)、γ-氨基丁酸(GABA)、甘氨酸(Gly)、牛磺酸(Tau)浓度;采用Aim Plex流式高通量多因子检测技术检测L3~L5节段脊髓组织内调节激活T细胞表达与分泌因子(RANTES)、单核细胞趋化蛋白(MCP-3)的含量;并观察GABAa受体拮抗剂(荷包牡丹碱)对CQ复方镇痛作用的影响。研究结果发现,CQ复方能够显著提高模型小鼠的MWT(P<0.01,P<0.05),降低L3~L5节段脊髓组织内兴奋性氨基酸Glu的含量(P<0.01,P<0.05),提高抑制性氨基酸GABA,Gly,Tau的含量(P<0.01,P<0.05),降低Glu/GABA比值(P<0.01,P<0.05),降低RANTES,MCP-3水平(P<0.05)。GABAa受体拮抗剂在2个时间点有意义地降低了CQ复方引起的MWT升高(P<0.05)。该研究结果表明,CQ复方对CIIMIP模型小鼠有显著的镇痛作用,其机制与调节中枢神经系统兴奋性氨基酸(EAA)/抑制性氨基酸(IAA)递质的平衡,部分激活GABAa受体,以及减少脊髓组织内促炎性细胞因子RANTES,MCP-3的释放有关。This study aimed to analyze the analgesic effect and related central mechanisms of CQ prescription on cancer invasion induced mirror image pain（ CIIMIP） in model mice. In the study,male BALB / c mice were randomly divided into normal group,operation control group（ injected with 0. 2 m L inactivated S180 sarcoma cell sap）,model group（ injected with 0. 2 m L S180 sarcoma cell sap on the right leg near the greater trochanter of femur） and CQ prescription low dose group（ intraperitoneally injected with CQ prescription 100 mg·kg-1on the basis of model mice）,CQ prescription middle dose group（ intraperitoneally injected with CQ prescription 150 mg·kg-1on the basis of model mice）,and CQ prescription high dose group（ intraperitoneally injected with CQ prescription200 mg·kg-1on the basis of model mice）. Mechanical withdraw threshold（ MWT） of the mirror image lateral hind paws were evaluated by Von Frey hairs before modeling and after surgery. The levels of glutamate（ Glu）,gamma aminobutyric acid（ GABA）,glycine（ Gly）,and taurine（ Tau） in the L3-L5 spinal cord were measured by the high performance liquid chromatography-fluorescence detector（ HPLC-FLD）; Aim Plex detection technology with multiple factors was used to detect the levels of regulated on activation in normal T-cell expressed and secreted（ RANTES）,monocyte chemoattractant protein（ MCP-3） in the L3-L5 spinal cord. Then we observed the influence of GABAa receptor antagonist（ Bicuculline） on analgesic effect of CQ prescription. The results indicated that CQ prescription could remarkably increase MWT of model mice（ P〈0. 01,P〈0. 05）,decrease the level of Glu（ P〈0. 01,P〈0. 05）,improve the levels of GABA,Gly,Tau（ P〈0. 01,P〈0. 05）,lower the ratio of Glu / GABA（ P〈0. 01,P〈0. 05）,and reduce the levels of RANTES,MCP-3（ P〈0. 05） in the L3-L5 spinal cord,and GABAa receptor antagonist significantly blocked the analgesic effect of CQ prescription at two time points（ P〈0. 05）

关 键 词：癌侵袭镜像痛 CQ复方 神经递质 GABAA受体 促炎性细胞因子 

分 类 号：R285.5[医药卫生—中药学] R-332[医药卫生—中医学]