CQ復(fù)方對(duì)骨癌痛模型大鼠的痛覺敏化干預(yù)作用及機(jī)制
本文選題:CQ復(fù)方 + 脛骨轉(zhuǎn)移性癌痛; 參考:《中國(guó)實(shí)驗(yàn)方劑學(xué)雜志》2017年22期
【摘要】:目的:研究CQ復(fù)方對(duì)大鼠骨癌痛模型的痛覺敏化干預(yù)作用及其相關(guān)機(jī)制。方法:將雌性Wistar大鼠隨機(jī)分為假手術(shù)組和手術(shù)組,分別進(jìn)行操作對(duì)照和Walker-256乳腺癌細(xì)胞移植于脛骨的轉(zhuǎn)移性癌痛造模手術(shù)。將造模成功的40只大鼠隨機(jī)分為模型組,CQ復(fù)方高、中、低劑量組(200,150,100 mg·kg~(-1))及加巴噴丁組(100 mg·kg~(-1)),每組8只大鼠。以Von frey纖維絲測(cè)定的機(jī)械縮足閾值(mechanical withdrawal threshold,MWT)作為大鼠疼痛行為學(xué)評(píng)價(jià)指標(biāo);采用微透析分析儀檢測(cè)腦脊液內(nèi)谷氨酸(glutamate,Glu),放射免疫法檢測(cè)脊髓L4~L6節(jié)段內(nèi)P物質(zhì)(substance P,SP)及β-內(nèi)啡肽(β-endorphin,β-EP)含量;采用Aim Plex流式高通量多因子檢測(cè)技術(shù)分析腫瘤局部組織中白細(xì)胞介素-12(interleukin-12,IL~(-1)2-P70),神經(jīng)生長(zhǎng)因子(β-nerve growth factor,β-NGF)含量。結(jié)果:與模型組相比,CQ復(fù)方各組及加巴噴丁組均明顯提高了大鼠的MWT,前者投藥30 min后MWT上升,60 min升高最明顯(P0.05,P0.01),CQ復(fù)方高、中、低劑量組之間其閾值升高呈量效依賴關(guān)系,且連續(xù)3 d投藥的鎮(zhèn)痛效果強(qiáng)于第1次投藥;與模型組相比,CQ復(fù)方及加巴噴丁降低了骨癌痛模型大鼠腦脊液中Glu,脊髓L4~L6節(jié)段中SP,β-EP和腫瘤局部組織中β-NGF水平(P0.05),提高了IL~(-1)2-P70的濃度(P0.05)。結(jié)論:CQ復(fù)方具有干預(yù)骨癌痛大鼠痛覺敏化行為學(xué)指標(biāo)的作用,強(qiáng)度與加巴噴丁相似;其機(jī)制可能與抑制中樞內(nèi)興奮性氨基酸類神經(jīng)遞質(zhì)Glu,肽類神經(jīng)調(diào)質(zhì)SP,β-EP及周圍組織β-NGF的水平、并促進(jìn)機(jī)體免疫反應(yīng)的IL~(-1)2-P70有關(guān)。
[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.
【作者單位】: 首都醫(yī)科大學(xué)附屬北京中醫(yī)醫(yī)院;中國(guó)中醫(yī)科學(xué)院醫(yī)學(xué)實(shí)驗(yàn)中心北京市中醫(yī)藥防治重大疾病基礎(chǔ)研究重點(diǎn)實(shí)驗(yàn)室;
【基金】:國(guó)家科技部國(guó)際科技合作專項(xiàng)(2010DFA31890) 中國(guó)中醫(yī)科學(xué)院自主選題研究項(xiàng)目(ZZ2013003)
【分類號(hào)】:R285.5;R-332
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