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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

发布时间:2018-06-07 14:34

  本文选题:癌侵袭镜像痛 + CQ复方 ; 参考:《中国中药杂志》2017年04期


【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(P0.01,P0.05),降低L3~L5节段脊髓组织内兴奋性氨基酸Glu的含量(P0.01,P0.05),提高抑制性氨基酸GABA,Gly,Tau的含量(P0.01,P0.05),降低Glu/GABA比值(P0.01,P0.05),降低RANTES,MCP-3水平(P0.05)。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(P0.05)。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。
[Abstract]:The purpose of this study was to investigate the analgesic effect of CQ compound on invasion induced mirror image CIIMIP model mice and its related central mechanism. The male BALB/c mice were randomly divided into normal group, Operation control group (0.2 mL inactivated S180 sarcoma cell fluid), model group (0.2 mL S180 sarcoma cell fluid injection at right leg trochanter), CQ compound low dose group (model 100 mg 路kg ~ (-1) CQ compound medium dose group (model 150 mg 路kg ~ (-1) In the high dose group (model 200mg / kg), Von Frey filament was used to measure the mechanical foot contraction threshold and mechanical withdrawal thresholdMWTA before and after the model, and the high performance liquid phase fluorescence (HPLC-FLDD) method was used to detect glutamate, 纬 -aminobutyrate GABAN, GABAN in the L3~L5 segment of spinal cord. The concentration of glycine, taurine Tau); The expression and secretion of regulatory activated T cells (RANTES), a monocyte chemoattractant protein (MCP-3), in L3~L5 segments of spinal cord were detected by Aim Plex flow high throughput multifactor assay. The effect of GABAa receptor antagonist (bicuculline) on CQ compound analgesia was observed. The results showed that CQ compound could significantly increase the level of MWTP 0.01 and P0.05, decrease the content of excitatory amino acid Glu in the spinal cord of L3~L5 segment and increase the content of inhibitory amino acid GABA Glycine Tau, decrease the ratio of Glu/GABA to Glu/GABA and decrease the level of RANTESm MCP-3 and the level of GABA A receptor. At two time points, the anti-agent significantly reduced the increase of MWT induced by CQ compound (P0. 05%). The results showed that CQ compound had a significant analgesic effect on CIIMIP model mice, and its mechanism was related to regulating the balance of excitatory amino acid (EAA) / inhibitory amino acid (EAA) transmitters in central nervous system (CNS) and partially activating GABAa receptors. And to reduce the release of the inflammatory cytokine RANTESN MCP-3 in spinal cord tissue.
【作者单位】: 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;
【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)
【分类号】:R285.5;R-332

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