神經(jīng)降壓素在大鼠脊髓背角的鎮(zhèn)痛作用及其機制
發(fā)布時間:2018-04-05 17:12
本文選題:神經(jīng)降壓素 切入點:鎮(zhèn)痛 出處:《第四軍醫(yī)大學》2005年博士論文
【摘要】:神經(jīng)降壓素(neurotensin,NT)是由13個氨基酸組成的神經(jīng)肽(pGlu-Leu-Tyr-Glu-Asn-Lys-Pro-Arg-Arg-Pro-Tyr-Ile-Leu-OH)。在中樞神經(jīng)系統(tǒng)內(nèi),NT作為神經(jīng)遞質(zhì)或調(diào)質(zhì)而發(fā)揮作用,其效應(yīng)包括降溫、鎮(zhèn)痛、調(diào)節(jié)多巴胺能傳遞和刺激垂體前葉激素釋放。微量注射實驗觀察到NT在參與痛覺反應(yīng)的多個腦區(qū)和通路調(diào)節(jié)傷害性信息的傳遞,包括杏仁核、下丘腦視前核、丘腦核團、中腦導水管周圍灰質(zhì)(PAG)以及延髓頭端腹內(nèi)側(cè)核群(RVM)。PAG和RVM是組成痛覺下行抑制系統(tǒng)的重要結(jié)構(gòu)。在RVM內(nèi),小劑量的NT發(fā)揮著易化疼痛的作用,而大劑量的NT才能發(fā)揮鎮(zhèn)痛作用。這種現(xiàn)象可能是因為中樞內(nèi)參與NT對痛覺調(diào)制的NT受體(NTR)不僅1種。目前已經(jīng)發(fā)現(xiàn)并克隆的NTR有3種,其中NTR1和NTR2是有7次跨膜結(jié)構(gòu)的G蛋白偶聯(lián)受體,介導NT的信號傳導;而NTR3的功能尚不清楚。 盡管NT在脊髓上位腦結(jié)構(gòu)中可能發(fā)揮鎮(zhèn)痛作用,但以往關(guān)于NT在脊髓是否具有鎮(zhèn)痛作用的行為學研究,沒有取得一致的結(jié)論。因此,本研究綜合運用形態(tài)學、電生理學和行為學方法探討了NT在脊髓水平對痛信息傳遞的作用及其機制。在脊髓背角淺層(Ⅰ、Ⅱ?qū)?內(nèi)可見密集的NT陽性胞體、纖維和終末以及散在分布的NTR2陽性胞體和纖維。
[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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