基于thermo TRP研究乳腺癌骨轉(zhuǎn)移大鼠癌性疼痛的發(fā)生機(jī)制
發(fā)布時間:2018-03-02 15:49
本文選題:腫瘤骨轉(zhuǎn)移 切入點:骨癌痛 出處:《南京中醫(yī)藥大學(xué)》2017年碩士論文 論文類型:學(xué)位論文
【摘要】:目的:明確腫瘤骨轉(zhuǎn)移疼痛(骨癌痛)具有冷刺激痛敏的癥狀特點;TRPA1、TRPM8參與腫瘤骨轉(zhuǎn)移疼痛敏感狀態(tài)的發(fā)生和維持機(jī)制。方法:選取健康4月齡SD雄性大鼠60只,體重350-450g,隨機(jī)分成骨癌痛模型組(僅造模,無藥物干預(yù))、模型-通道阻滯劑干預(yù)組(造模2周后應(yīng)用TRPA1、TRPM8拮抗劑干預(yù)的大鼠)、空白對照組、假手術(shù)組。分別于造模前1周、造模后2、4、6、8周,檢測冷刺激痛閾;并在造模后8周后,運用Western Blot、Real-time PCR、免疫熒光等技術(shù)檢測各組大鼠背根神經(jīng)節(jié)組織TRPA1、TRPM8蛋白及mRNA表達(dá),并觀察腫瘤種植部病理切片形態(tài)。結(jié)果:病理組織切片HE染色可見骨癌痛模型組大鼠腫瘤細(xì)胞種植部周圍骨組織中腫瘤細(xì)胞簇集浸潤和廣泛炎性反應(yīng)。造模后2周,模型組大鼠冷刺激痛閾對比正常組顯著降低,且至造模后8周仍維持在相對較低水平(P0.05)。TRPA1和TRPM8的選擇性通道阻斷劑能夠有效改善骨癌痛大鼠的冷刺激痛敏(P0.05)。假手術(shù)組大鼠的冷刺激痛閾對比空白對照組無顯著差異(P0.05)。骨癌痛大鼠背根神經(jīng)節(jié)中TRPA1、TRPM8蛋白及mRNA表達(dá)均較空白對照組顯著增高(P0.05)。假手術(shù)組背根神經(jīng)節(jié)中TRPA1、TRPM8蛋白及mRNA表達(dá)對比空白對照組并無顯著差異(P0.05)。結(jié)論:腫瘤骨轉(zhuǎn)移的癌性疼痛具有冷刺激痛敏的癥狀特點;TRPA1、TRPM8與腫瘤骨轉(zhuǎn)移所致骨癌痛的冷刺激痛敏具有高度相關(guān)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.
【學(xué)位授予單位】:南京中醫(yī)藥大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R737.9
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