基于thermo TRP研究乳腺癌骨转移大鼠癌性疼痛的发生机制

发布时间：2018-03-02 15:49

  本文选题：肿瘤骨转移　切入点：骨癌痛　出处：《南京中医药大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:明确肿瘤骨转移疼痛(骨癌痛)具有冷刺激痛敏的症状特点;TRPA1、TRPM8参与肿瘤骨转移疼痛敏感状态的发生和维持机制。方法:选取健康4月龄SD雄性大鼠60只,体重350-450g,随机分成骨癌痛模型组(仅造模,无药物干预)、模型-通道阻滞剂干预组(造模2周后应用TRPA1、TRPM8拮抗剂干预的大鼠)、空白对照组、假手术组。分别于造模前1周、造模后2、4、6、8周,检测冷刺激痛阈;并在造模后8周后,运用Western Blot、Real-time PCR、免疫荧光等技术检测各组大鼠背根神经节组织TRPA1、TRPM8蛋白及mRNA表达,并观察肿瘤种植部病理切片形态。结果:病理组织切片HE染色可见骨癌痛模型组大鼠肿瘤细胞种植部周围骨组织中肿瘤细胞簇集浸润和广泛炎性反应。造模后2周,模型组大鼠冷刺激痛阈对比正常组显著降低,且至造模后8周仍维持在相对较低水平(P0.05)。TRPA1和TRPM8的选择性通道阻断剂能够有效改善骨癌痛大鼠的冷刺激痛敏(P0.05)。假手术组大鼠的冷刺激痛阈对比空白对照组无显著差异(P0.05)。骨癌痛大鼠背根神经节中TRPA1、TRPM8蛋白及mRNA表达均较空白对照组显著增高(P0.05)。假手术组背根神经节中TRPA1、TRPM8蛋白及mRNA表达对比空白对照组并无显著差异(P0.05)。结论:肿瘤骨转移的癌性疼痛具有冷刺激痛敏的症状特点;TRPA1、TRPM8与肿瘤骨转移所致骨癌痛的冷刺激痛敏具有高度相关性。
[Abstract]:Objective: to investigate the symptoms of pain of bone metastases (bone cancer pain) with cold stimulation. Methods: 60 male SD rats aged 4 months were selected to study the mechanism of TRPA1TRPM8 involved in the pathogenesis and maintenance of pain sensitivity of tumor bone metastases. Methods: a total of 60 male Sprague-Dawley rats (SD) aged 4 months were enrolled in this study. The rats weighing 350-450 g were randomly divided into two groups: model group (model only, no drug intervention, model-channel blocker intervention group) (rats treated with TRPA1-TRPM8 antagonist after 2 weeks, blank control group, sham-operation group). After 8 weeks, the pain threshold of cold stimulation was detected, and the expression of TRPA1 and TRPM8 protein and mRNA in the dorsal root ganglion of rats in each group were detected by Western blotl Real-time PCR and immunofluorescence. Results: the tumor cell cluster infiltration and extensive inflammatory reaction were observed in the bone tissue around the implant of tumor cells in the model group by HE staining. The pain threshold of cold stimulation in the model group was significantly lower than that in the normal group. In addition, the selective channel blockers of P0.05N. TRPA1 and TRPM8 maintained at a relatively low level at 8 weeks after modeling could effectively improve the cold stimulation pain sensitivity of rats with bone cancer pain. There was no significant difference in cold stimulation pain threshold of sham-operated rats compared with the blank control group. The expression of TRPA1-TRPM8 protein and mRNA in the dorsal root ganglion of rats with pain of bone cancer was significantly higher than that of the blank control group (P 0.05). There was no significant difference in the expression of TRPA1-TRPM8 protein and mRNA in the dorsal root ganglion of the sham operation group compared with the blank control group. Conclusion: the tumor bone transfer. There was a high correlation between TRPA 1 TRPM8 and cold stimulation pain induced by bone metastasis.
【学位授予单位】：南京中医药大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.9

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