MC4R介导神经病理性疼痛的传导机制

发布时间：2018-05-15 02:18

本文选题：HS014 + NF-κB　；参考：《青岛大学》2015年博士论文

【摘要】：目的观察HSO14对脊髓背角和脊髓背根神经节(DRG)中NF-κB的影响,探讨MC4R和NF-κB之间关系。方法先予以大鼠鞘内置管成功后,取坐骨神经结扎(CCI)模型,将成熟雄性SD大鼠72只分为四组,假手术组(sham组),将大鼠坐骨神经暴露后不予任何处理,CCI组,只结扎坐骨神经,H组,CCI后鞘内注射MC4R拮抗剂HS014,10μg/天,持续7天。P组,鞘内注射NF-κB抑制剂PDTC,2 ug/天,持续7天。分别于术后3天、7天、14天观察大鼠的热痛阈,免疫组化及Western blot检测L5-6脊髓背角及其背根神经节MC4R和NF-κB变化。结果CCI组较假手术组术后各时间点热痛阈显著下降(p0.01),MC4R,NF-κB于CCI术后表达相对sham组明显增多(p0.01)。H组较sham组热痛阈下降,但比CCI组显著上升(p0.05),MC4R,NF-κB较CCI组显著下降(p0.05)。P组较CCI组热痛阈显著上升(p0.05),MC4R无显著变化而NF-κB显著下降(p0.05)。结论HS014通过抑制MC4R进而抑制NF-κB的激活而减轻神经病理性疼痛,神经损伤所致神经病理性疼痛中NF-κB可能是MC4R的一个下游信号通路。
[Abstract]:Objective to observe the effect of HSO14 on NF- 魏 B in dorsal horn and dorsal root ganglion of spinal cord, and to explore the relationship between MC4R and NF- 魏 B. Methods 72 adult male SD rats were divided into four groups after successful intrathecal catheterization of sciatic nerve ligation of the sciatic nerve (CCI). Sham group was used as sham group. The sciatic nerve was exposed without any treatment in CCI group. In group H, 10 渭 g / day MC4R antagonist HS014A was injected intrathecally after ligation of the sciatic nerve. The rats in group P were given intrathecal injection of NF- 魏 B inhibitor PDT Con for 2 ug/ days for 7 days. The thermal pain threshold, the changes of MC4R and NF- 魏 B in the dorsal horn of L5-6 spinal cord and its dorsal root ganglion were detected by immunohistochemistry and Western blot. Results compared with the sham operation group, the thermal pain threshold in CCI group was significantly lower than that in the sham operation group. The expression of NF- 魏 B in MC4RN- 魏 B in CCI group was significantly higher than that in sham group. Compared with sham group, the thermal pain threshold in CCI group was significantly lower than that in sham group. But compared with CCI group, there was a significant increase in p0.05RN NF- 魏 B and a significant decrease in P0.05N. P group compared with CCI group. The thermal pain threshold in group P was significantly higher than that in group CCI. There was no significant change in P0.05C4R, but NF- 魏 B decreased significantly (p0.05N). Conclusion HS014 alleviates neuropathic pain by inhibiting MC4R and then inhibiting the activation of NF- 魏 B. NF- 魏 B may be a downstream signal pathway of MC4R in neuropathic pain caused by nerve injury.
【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R402

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