炎性疼痛大鼠海马5-HT水平、5-HT2A受体mRNA和BDNFmRNA的表达和作用研究及度洛西汀的干预作用

发布时间：2018-05-25 11:10

本文选题：炎性疼痛 + 海马　；参考：《济宁医学院》2017年硕士论文

【摘要】：目的:疼痛引起的不愉快的情绪可以影响机体对疼痛的感知。海马体是大脑边缘系统的重要组成部分,参与处理和调整疼痛刺激,尤其是疼痛的情绪-动机部分。海马的形态可塑性的变化以及海马内神经化学物质的改变都与疼痛有着密切的联系,但是具体机制没有完全清楚。其中5-羟色胺(5-hydroxytryptamine,5-HT)以及在5-HT2A受体都参与疼痛的调解。脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)能够调节海马内神经元的可塑性变化。因此本实验的目的是:(1)探讨炎性疼痛大鼠海马内5-HT、5-HT2A受体mRNA和BDNFmRNA的表达的变化及其作用;(2)探讨度洛西汀对炎性大鼠海马内5-HT、5-HT2A受体mRNA及BDNFmRNA表达的影响;(3)探讨5-HT与BDNF之间的关系。方法:将72只成年的雄性SD(Sprague-Dawley)大鼠随机分为对照组,实验组:炎性疼痛模型组、炎性疼痛模型+生理盐水灌胃组和炎性疼痛模型+度洛西汀灌胃组,每组各18只。炎症疼痛模型是向大鼠左侧的足底皮下注射完全弗氏佐剂(Complete Freund’s Adjuvant,CFA)和生理盐水(1:1)混合溶剂100μl。度洛西汀(10mg/(kg.d))灌胃2周,生理盐水同等剂量灌胃2周。在建模前及处理2周后采用电子测痛仪检测大鼠左侧足底50%缩足阈值(paw withdrawal threshold,PWT)的变化,用糖水偏爱实验和强迫游泳实验检测大鼠抑郁样行为,采用RT-PCR检测不同组间大鼠海马内5-HT2A受体mRNA和BDNFmRNA的表达,ELISA检测海马中5-HT的变化。结果:四组大鼠在处理前,50%PWT差异无统计学意义。2周后炎性疼痛模型组的50%PWT和糖水消耗率与对照组比较,痛阈和糖水消耗率降低,不动时间增加,差异有统计学意义(P0.05)。炎性疼痛模型+度洛西汀灌胃组与炎性疼痛模型+生理盐水灌胃组相比的50%PWT升高(P0.01),糖水消耗率升高(P0.05),不动时间下降(P0.01)。炎性疼痛模型组与对照组相比较,海马中的5-HT降低(P0.05),海马中5-HT2A受体mRNA的表达均值降低,但差异无统计学意义(P0.05),BDNFmRNA的表达降低(P0.05)。炎性疼痛模型+度洛西汀灌胃组与炎性疼痛模型+生理盐水灌胃组比较,海马中的5-HT上升(P0.01),海马中5-HT2A受体mRNA和BDNFmRNA的表达都升高(P0.05)。结论:慢性炎性疼痛大鼠出现的痛阈下降和抑郁样表现可能与海马内5-HT水平和BDNFmRNA的表达下降有关;度洛西汀可以提高慢性炎性疼痛大鼠的痛阈,改善抑郁样行为,其机制可能通过海马中5-HT、5-HT2A受体mRNA和BDNFmRNA的表达升高发挥作用;5-HT可能通过其2A受体参与BDNF的调节。
[Abstract]:Objective: pain-induced unpleasant emotions can affect the body's perception of pain. The hippocampus is an important component of the limbic system of the brain, involved in the processing and adjustment of pain stimuli, especially the emotion-motivational part of pain. The morphological plasticity of the hippocampus and the changes of neurochemicals in the hippocampus are closely related to pain, but the mechanism is not completely clear. Serotonin 5-hydroxytryptamine 5-HT) and the 5-HT2A receptor are involved in pain mediation. Brain-derived neurotrophic factor (BDNF) can regulate the plasticity of hippocampal neurons. The purpose of this study was to investigate the expression of 5-HT-5-HT2A receptor mRNA and 5-HT2A receptor mRNA and BDNFmRNA in hippocampus of rats with inflammatory pain. (2) to explore the effect of doxetine on the expression of 5-HT-5-HT2A receptor mRNA and BDNFmRNA in the hippocampus of inflammatory rats.) to explore the relationship between 5-HT and BDNF. Methods: Seventy-two adult SD rats were randomly divided into control group (n = 18), inflammatory pain model group (n = 18) and inflammatory pain model group (n = 18). The inflammatory pain model was induced by subcutaneous injection of complete Freund's Adjuvant (100 渭 l) and normal saline (1: 1) into the left plantar of rats. Doxicetine 10 mg / kg 路dl) for 2 weeks and saline at the same dose for 2 weeks. Before modeling and 2 weeks after treatment, the changes of paw withdrawal threshold in left plantar of rats were detected by electronic pain measuring instrument. The depressive behavior of rats was detected by sugar water preference experiment and forced swimming experiment. The expression of 5-HT2A receptor mRNA and BDNFmRNA in hippocampus of different groups was detected by RT-PCR and the changes of 5-HT in hippocampus were detected by Elisa. Results: compared with the control group, the pain threshold and glucose water consumption rate in the inflammatory pain model group were lower than those in the control group, and the immobility time was increased. The difference was statistically significant (P 0.05). Compared with the inflammatory pain model group, the 50%PWT of the inflammatory pain model group was higher than that of the saline group, the consumption rate of sugar water was increased (P 0.05), and the time of immobility was decreased (P 0.01). In the inflammatory pain model group, compared with the control group, the expression of 5-HT in the hippocampus decreased P0.05A, and the average expression of 5-HT2A receptor mRNA in the hippocampus decreased, but there was no significant difference between the two groups. Compared with the saline group, the expression of 5-HT in hippocampus and the expression of 5-HT2A receptor mRNA and BDNFmRNA in hippocampus were increased in the inflammatory pain model group compared with that in the saline group. Conclusion: the decrease of pain threshold and depression-like manifestation in chronic inflammatory pain rats may be related to the decrease of 5-HT level and BDNFmRNA expression in hippocampus, and doloxetine can increase the pain threshold and improve depressive behavior in chronic inflammatory pain rats. The mechanism of 5-HT may play a role in the regulation of BDNF by increasing the expression of 5-HT-5-HT2A receptor mRNA and BDNFmRNA in hippocampus.
【学位授予单位】：济宁医学院
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R402

【参考文献】