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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 understand the analgesic effect of CQ compound on mice with cancer invasion induced mirror image pain (CIIMIP) and its related central mechanism. Male BALB / c mice were randomly divided into normal group, control group (injection of 0.2 m L inactivated S180 sarcoma cell solution), model group (0.2 m L S180 sarcoma fluid injected into the right trochanter) The rats in the CQ compound low-dose group (model +100 mg · kg -1, ip), CQ compound middle dose group (model + 150 mg · kg -1, ip), CQ compound high dose group 200 mg · kg -1, ip). The mechanical withdrawal threshold (MWT) of the mirror-side hindpaw was measured before and after modeling with Von Frey filaments. High-performance liquid-fluorescence The concentrations of Glu, GABA, Gly and Tau in the L3 ~ L5 spinal cord segments were measured by HPLC-FLD. Aim Plex flow cytometry The levels of MCP-3 and MCP-3 in L3 ~ L5 spinal cord tissue were detected by factor test, and the effects of GABAa receptor antagonist (bicuculline) Effect of CQ Compound Analgesia. The results showed that CQ compound could significantly increase the MWT (P <0.01, P <0.05) and decrease the content of excitatory amino acid Glu (P <0.01, P <0.05) in L3 ~ L5 spinal cord The levels of GABA, Gly and Tau were decreased (P <0.01, P <0.05), and the ratio of Glu / GABA was decreased (P <0.01, P <0.05) and the levels of RANTES and MCP-3 were decreased (P <0.05). GABAa receptor antagonists significantly reduced CQ compound-induced elevated MWT at 2 time points (P <0.05). The results show that CQ compound has significant analgesic effect on CIIMIP model mice, and its mechanism is related to the regulation of central nervous system excitatory amino acid (EAA) / inhibitory amino acid (IAA) transmitter balance, partially activating GABAa receptor, As well as reducing the release of proinflammatory cytokines RANTES, MCP-3 in spinal cord tissue.