TRPV1下调对神经病理性疼痛的保护作用及其作用机制研究

发布时间：2018-06-15 06:45

  本文选题：神经病理性疼痛 + 辣椒素受体　； 参考：《福建医科大学》2014年硕士论文

【摘要】：目的：研究辣椒素受体（TRPV1）在大鼠创伤性神经病理痛中的表达变化与作用；探讨TRPV1拮抗剂是否有助于减轻疼痛。TRPV1的下调是否通过再生基因(PAP-I)起作用； 方法：将75只SD雄性大鼠（180g-220g）随机分为假手术组、试验组A与实验组B，A、B两组根据术后时间点再细分为7组（术前1d，1d，3d，5d，7d，14d，21d，n=5）。建立坐骨神经慢性压迫性损伤模型(CCI)[1]。B组在术后每天用TRPV1特异性拮抗剂SB705498（30mg/kg）灌胃给药。A、B两组在各实验预期时间点用Von frey针丝刺激大鼠术侧趾蹼进行痛阈值检测，随后处死大鼠取L4-L5段脊髓的背根神经节分别用免疫组化，RT-PCR，Western-blot等方法测量TRPV1及PAP-I的表达水平，记录并分析两者与神经行为改变之间的相关性。 结果： CCI模型可明显致大鼠机械痛敏，PAP-I在A、B两组表达无统计学意义（P＞0.05），术后第1d两组即有表达，在术后5d达到峰值，持续14d逐渐恢复到正常水平。假手术组TRPV1表达与A组术前无明显差异（P＞0.05），术后有统计学差异（P＜0.05），A组TRPV1在术后开始表达并在第7d达到高峰，在3w后表达恢复到正常水平，其表达情况与痛阈值成正相关（r=0.79）；B组给予其特异性拮抗剂后TRPV1表达较A组明显降低（P＜0.05），大鼠神经痛的症状得到显著改善。 结论：TRPV1参与神经病理性疼痛的形成，应用TRPV1特异性拮抗剂SB705498有助于改善神经痛的症状。PAP-I在神经病理性疼痛的发生发展过程中表达上升，，表达越程度越高，疼痛越明显。阻断TRPV1并不会对PAP-I表达造成影响。
[Abstract]:Objective: to investigate the expression and role of capsaicin receptor TRPV1 in traumatic neuropathic pain in rats, and to explore whether the down-regulation of TRPV1 may play a role in alleviating the pain by regeneration gene PAP-I. Methods: 75 Sprague-Dawley male rats were randomly divided into sham-operation group (n = 75). Group A and group B were subdivided into 7 groups according to the postoperative time points. To establish the model of chronic compression injury of sciatic nerve (CCI) [1]. Group B was given intragastric administration of TRPV1 specific antagonist SB70549830mg / kg every day after operation. The expression of TRPV1 and PAP-I in dorsal root ganglion (DRG) of L4-L5 spinal cord were measured by immunohistochemical RT-PCR and Western-blot respectively. The correlation between the expression of TRPV1 and PAP-I was recorded and analyzed. Results: the expression of PAP-I in the two groups was not statistically significant (P > 0.05). The expression of PAP-I in the first day after operation reached the peak value on the 5th day after operation, and gradually returned to the normal level on the 14th day. There was no significant difference in the expression of TRPV1 between group A and group A before operation (P > 0.05), but there was significant difference between group A and group A (P < 0.05). The expression of TRPV1 in group A began to express after operation and reached its peak on the 7th day. The expression of TRPV1 returned to normal level after 3 weeks. The expression of TRPV1 was positively correlated with the pain threshold. The expression of TRPV1 in group B was significantly lower than that in group A (P < 0.05), and the symptoms of neuralgia were significantly improved. ConclusionTwo one TRPV1 is involved in the formation of neuropathic pain. The application of TRPV1 specific antagonist SB705498 can improve the symptoms of neuralgia. The expression of PAP-I in the process of neuropathic pain is increased. The higher the expression, the more obvious the pain. Blocking TRPV1 did not affect the expression of PAP-I.
【学位授予单位】：福建医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R741


本文编号：2021085