CAJ | 학술논문

目的：研究加巴喷丁对Walker-256乳腺癌细胞构建的大鼠胫骨转移性癌痛模型的镇痛作用及其机制。方法雌性wistar大鼠30只，随机分为假手术组（sham）、模型组（model）和加巴喷丁组（GBP，100 mg/kg），每组10只；分别进行操作对照和胫骨转移性癌痛造模手术。以机械痛缩足域值和影像学观察作为大鼠疼痛行为学的评价指标；分别采用微透析分析仪 ISCUSFflex Microdialysis Analyzer、放射免疫法、流式多因子检测技术，测定脑脊液中谷氨酸（Glutamate，Glu）、脊髓中P物质（Substance P，SP）及肿瘤局部组织中白细胞介素-12/P70（Interleukin-12/p70，IL-12P70）、γ干扰素（Interferon-γ，IFN-γ）及β-神经生长因子（β-nerve growth factor，β-NGF）的含量。结果与假手术组相比，手术组胫骨转移性癌痛模型大鼠机械痛缩足域值明显下降，影像学观察到骨质破坏，脑脊液中Glu、脊髓中SP水平明显升高（P＜0.01，P＜0.05），肿瘤组织中IL-12P70、IFN-γ水平明显降低而β-NGF水平明显升高（P＜0.05）。与模型组相比，加巴喷丁给药后30 min大鼠机械痛缩足阈值开始上升，60～300 min明显升高（均P＜0.01）。加巴喷丁显著降低了骨癌痛大鼠脑脊液中Glu、脊髓中SP浓度（P＜0.01，P＜0.05），提高了大鼠肿瘤组织中IL-12P70和IFN-γ水平，降低了β-NGF浓度（P＜0.05）。结论加巴喷丁可减轻骨癌痛大鼠的疼痛行为学指标，其镇痛机制可能与抑制中枢兴奋性氨基酸、痛感调质及周围神经生长因子水平、增强外周的免疫作用有关。
목적：연구가파분정대Walker-256유선암세포구건적대서경골전이성암통모형적진통작용급기궤제。방법자성wistar대서30지，수궤분위가수술조（sham）、모형조（model）화가파분정조（GBP，100 mg/kg），매조10지；분별진행조작대조화경골전이성암통조모수술。이궤계통축족역치화영상학관찰작위대서동통행위학적평개지표；분별채용미투석분석의 ISCUSFflex Microdialysis Analyzer、방사면역법、류식다인자검측기술，측정뇌척액중곡안산（Glutamate，Glu）、척수중P물질（Substance P，SP）급종류국부조직중백세포개소-12/P70（Interleukin-12/p70，IL-12P70）、γ간우소（Interferon-γ，IFN-γ）급β-신경생장인자（β-nerve growth factor，β-NGF）적함량。결과여가수술조상비，수술조경골전이성암통모형대서궤계통축족역치명현하강，영상학관찰도골질파배，뇌척액중Glu、척수중SP수평명현승고（P＜0.01，P＜0.05），종류조직중IL-12P70、IFN-γ수평명현강저이β-NGF수평명현승고（P＜0.05）。여모형조상비，가파분정급약후30 min대서궤계통축족역치개시상승，60～300 min명현승고（균P＜0.01）。가파분정현저강저료골암통대서뇌척액중Glu、척수중SP농도（P＜0.01，P＜0.05），제고료대서종류조직중IL-12P70화IFN-γ수평，강저료β-NGF농도（P＜0.05）。결론가파분정가감경골암통대서적동통행위학지표，기진통궤제가능여억제중추흥강성안기산、통감조질급주위신경생장인자수평、증강외주적면역작용유관。
Objective To study the analgesic effect and mechanism of gabapentin on tibia metastatic cancer pain rat model constructed by walker-256 breast cancer cells.Methods 30 Female wistar rats were randomly divided into sham group,model group and GBP group(100 mg/kg),each group had 10 rats.Sham operation were used as operation control and tibia metastatic cancer pain operation were done separately.Paw withdrawal mechanical threshold and observation of X-ray were used to evaluate rats’pain behavior.ISCUS biochemical method,radioimmunoassay,and streaming multi-factor detection technique were used to detect glutamate level of cerebrospinal fluid,substance P level in the spinal cord and expression of IL-12P70,IFN-γ,β-NGF in the tumor tissue.Results Compared with sham group,paw withdrawal mechanical threshold of tibia metastatic rat model in operaion group were decreased significantly,and X-ray showed bone destruction,the glutamate level of cerebrospinal fluid and substance P level in the spinal cord were increased significantly(P<0.01 or P<0.05).IL-12P70 and IFN-γlevels were significantly lower andβ-NGF level was higher than that in sham group (P<0.05).Compared with model group,paw withdrawal mechanical threshold of rats in gabapentin group began to rise in 30 min after administration,and peaked in 60~300 min(P<0.01).Gabapentin reduced the glutamate level of cerebrospinal fluid,substance P level in the spinal cord andβ-NGF level of tumor tissue concentrations significantly(P<0.01 or P<0.05),but increased IL-12P70 and IFN-γlevels of tumor tissue.Conclusion Gabapentin can relieve the bone cancer pain of rat model.Its analgesic mechanism may lie indecreasing the levels of central excitatory amino acids,pain-associated neuromodulator and the nerve growth factor,and enhancing the peripheral immune function.