神经降压素在大鼠脊髓背角的镇痛作用及其机制

发布时间：2018-04-05 17:12

  本文选题：神经降压素　切入点：镇痛　出处：《第四军医大学》2005年博士论文

【摘要】：神经降压素(neurotensin,NT)是由13个氨基酸组成的神经肽(pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH)。在中枢神经系统内,NT作为神经递质或调质而发挥作用,其效应包括降温、镇痛、调节多巴胺能传递和刺激垂体前叶激素释放。微量注射实验观察到NT在参与痛觉反应的多个脑区和通路调节伤害性信息的传递,包括杏仁核、下丘脑视前核、丘脑核团、中脑导水管周围灰质(PAG)以及延髓头端腹内侧核群(RVM)。PAG和RVM是组成痛觉下行抑制系统的重要结构。在RVM内,小剂量的NT发挥着易化疼痛的作用,而大剂量的NT才能发挥镇痛作用。这种现象可能是因为中枢内参与NT对痛觉调制的NT受体(NTR)不仅1种。目前已经发现并克隆的NTR有3种,其中NTR1和NTR2是有7次跨膜结构的G蛋白偶联受体,介导NT的信号传导;而NTR3的功能尚不清楚。 尽管NT在脊髓上位脑结构中可能发挥镇痛作用,但以往关于NT在脊髓是否具有镇痛作用的行为学研究,没有取得一致的结论。因此,本研究综合运用形态学、电生理学和行为学方法探讨了NT在脊髓水平对痛信息传递的作用及其机制。在脊髓背角浅层(Ⅰ、Ⅱ层)内可见密集的NT阳性胞体、纤维和终末以及散在分布的NTR2阳性胞体和纤维。
[Abstract]:NT acts as a neurotransmitter or modulator in the central nervous system. Its effects include cooling, analgesia, regulating dopamine transmission and stimulating the release of anterior pituitary hormone.Microinjection experiments showed that NT regulates the transmission of nociceptive information in multiple brain regions and pathways involved in pain response, including amygdala, hypothalamic preoptic nucleus and thalamic nucleus.The periaqueductal gray matter (PAG) and the rostral ventromedial nucleus of the medulla oblongata (RVMN. PAG and RVM) are important structures of the pain downlink suppression system.In RVM, low dose NT plays the role of pain facilitation, while high dose NT can play analgesic effect.This phenomenon may be due to more than one NT receptor involved in NT modulation of pain.Three kinds of NTR have been identified and cloned, among which NTR1 and NTR2 are G-protein-coupled receptors with transmembrane structure for seven times, which mediate the signal transduction of NT, but the function of NTR3 is not clear.Although NT may play an analgesic role in the epigastric structure of the spinal cord, previous behavioral studies on whether NT has analgesic effect in the spinal cord have not reached a consistent conclusion.Therefore, the effect of NT on pain information transmission at spinal cord level and its mechanism were studied by morphological, electrophysiological and behavioral methods.In the superficial layer of the dorsal horn of the spinal cord (layer 鈪，

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