CQ复方对骨癌痛模型大鼠的痛觉敏化干预作用及机制

发布时间：2018-05-02 07:44

本文选题：CQ复方 + 胫骨转移性癌痛　；参考：《中国实验方剂学杂志》2017年22期

【摘要】：目的:研究CQ复方对大鼠骨癌痛模型的痛觉敏化干预作用及其相关机制。方法:将雌性Wistar大鼠随机分为假手术组和手术组,分别进行操作对照和Walker-256乳腺癌细胞移植于胫骨的转移性癌痛造模手术。将造模成功的40只大鼠随机分为模型组,CQ复方高、中、低剂量组(200,150,100 mg·kg~(-1))及加巴喷丁组(100 mg·kg~(-1)),每组8只大鼠。以Von frey纤维丝测定的机械缩足阈值(mechanical withdrawal threshold,MWT)作为大鼠疼痛行为学评价指标;采用微透析分析仪检测脑脊液内谷氨酸(glutamate,Glu),放射免疫法检测脊髓L4~L6节段内P物质(substance P,SP)及β-内啡肽(β-endorphin,β-EP)含量;采用Aim Plex流式高通量多因子检测技术分析肿瘤局部组织中白细胞介素-12(interleukin-12,IL~(-1)2-P70),神经生长因子(β-nerve growth factor,β-NGF)含量。结果:与模型组相比,CQ复方各组及加巴喷丁组均明显提高了大鼠的MWT,前者投药30 min后MWT上升,60 min升高最明显(P0.05,P0.01),CQ复方高、中、低剂量组之间其阈值升高呈量效依赖关系,且连续3 d投药的镇痛效果强于第1次投药;与模型组相比,CQ复方及加巴喷丁降低了骨癌痛模型大鼠脑脊液中Glu,脊髓L4~L6节段中SP,β-EP和肿瘤局部组织中β-NGF水平(P0.05),提高了IL~(-1)2-P70的浓度(P0.05)。结论:CQ复方具有干预骨癌痛大鼠痛觉敏化行为学指标的作用,强度与加巴喷丁相似;其机制可能与抑制中枢内兴奋性氨基酸类神经递质Glu,肽类神经调质SP,β-EP及周围组织β-NGF的水平、并促进机体免疫反应的IL~(-1)2-P70有关。
[Abstract]:Aim: to study the effect of CQ compound on pain sensitization of bone cancer in rats and its related mechanism. Methods: female Wistar rats were randomly divided into sham operation group and operation group. The Walker-256 breast cancer cells transplanted to the tibia were used to model the metastatic cancer pain. Forty successful rats were randomly divided into two groups: the model group with high, middle and low doses of CQ (200150mg / kg) and the gabapentin group (n = 8) and the control group (n = 8, n = 8 in each group) and the control group (n = 8), and the control group (n = 8). The mechanical withdrawal thresholdMWTs measured by Von frey filament were used as the evaluation index of pain behavior in rats, and the contents of substance P substance (SP) and 尾 -endorphin (尾 -endorphin, 尾 -EP) in L4~L6 segment of spinal cord were detected by microdialysis analyzer and radioimmunoassay (RIA) in cerebrospinal fluid (CSF), glutamate (Glu) in cerebrospinal fluid (CSF), substance P substance (SP) and 尾 -endorphin (尾 -EP) in L4~L6 segment of spinal cord. The content of interleukin-12 (IL-12) and nerve growth factor (尾 -NGF) in local tumor tissue was analyzed by Aim Plex flow high throughput multifactor assay. Results: compared with the model group, the MWTs were significantly increased in the CQ compound group and the gabapentin group. After 30 min of administration of the former, the increase of 60 min of MWT was the most obvious. The threshold of the CQ compound was increased in a dose-dependent manner between the middle and low dose groups, and there was a dose-effect relationship between the middle and low dose groups. Compared with the model group, CQ compound and gabapentin decreased the levels of IL~(-1)2-P70 in CSF, SPU, 尾 -EP and 尾 -NGF in the L4~L6 segment of spinal cord and local tumor tissue, and increased the concentration of IL~(-1)2-P70. Conclusion the effect of the compound: CQ is similar to that of gabapentin, and its mechanism may be related to the inhibition of the levels of excitatory amino acid neurotransmitters Glu, peptide neuromodulating SPand 尾 -EP and 尾 -NGF in the peripheral tissues of rats with bone cancer pain. And promote the immune response of the body related to IL~(-1)2-P70.
【作者单位】：首都医科大学附属北京中医医院;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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