炎症大鼠下丘脑弓状核神经元敏感化的谷氨酸受体机制

发布时间：2018-05-04 18:02

本文选题：弓状核 + NMDA受体　；参考：《苏州大学》2010年硕士论文

【摘要】：目的:本实验旨在研究在外周炎症时下丘脑弓状核(hypothalamic arcuate nucleus, ARC)产生中枢敏感化及其谷氨酸受体机制和受体后信号转导。方法:建立完全弗氏佐剂(complete Freund’s adjuvant,CFA)炎症痛模型;用玻璃微电极在体细胞外记录ARC神经元的自发放电及其对伤害性刺激的反应;侧脑室内微量注射MK-801(NMDA受体非竞争性拮抗剂)、Ro25-6981(NMDA受体NR2B亚单位拮抗剂)、CNQX(非NMDA受体拮抗剂)、PP2(Src家族蛋白酪氨酸激酶抑制剂)、GF109203X(蛋白激酶C抑制剂),观察阻断促离子型谷氨酸受体或受体后激酶磷酸化对正常大鼠及CFA炎症大鼠ARC神经元对伤害性刺激反应的影响。结果:(1)ARC神经元的自发放电频率,炎症大鼠明显高于正常大鼠;(2)ARC神经元对伤害性刺激的反应,炎症大鼠明显高于正常大鼠;(3)侧脑室内微量注射MK-801(20nmol)、Ro25-6981(6nmol)、CNQX(20nmol)可抑制正常大鼠和炎症大鼠ARC痛特异性神经元对伤害性刺激的反应;(4)侧脑室内微量注射PP2(5nmol)、GF109203X(0.04nmol)可抑制正常大鼠和炎症大鼠ARC痛特异性神经元对伤害性刺激的反应。结论:(1)外周CFA炎症时,ARC神经元的兴奋性提高,对伤害性刺激的反应增强;(2)中枢NMDA受体及其NR2B亚单位、非NMDA受体参与正常大鼠和CFA炎症大鼠ARC神经元对伤害性刺激的反应;(3)脑内Src蛋白酪氨酸激酶和蛋白激酶C可能参与正常大鼠和CFA炎症大鼠ARC痛特异性神经元对伤害性刺激的反应;(4)ARC作为脊髓以上水平调节痛觉的一个高位中枢,在外周炎症时也可产生中枢敏感化。
[Abstract]:Aim: to study the central sensitization of hypothalamic arcuate nucleus in hypothalamic arcuate nucleus (Arc) and its glutamate receptor mechanism and postreceptor signal transduction during peripheral inflammation. Methods: the inflammatory pain model of complete Freund adjuvant complete Freund's adjuvant was established, and the spontaneous discharges of ARC neurons and their responses to nociceptive stimuli were recorded by glass microelectrode in vitro. Microinjection of MK-801(NMDA receptor noncompetitive antagonist Ro25-6981NMDA receptor NR2B subunit antagonist CNQXPP2Src family protein tyrosine kinase inhibitor PP2Src family protein tyrosine kinase inhibitor (protein kinase C inhibitor, protein kinase C) to observe the blocking of ion-promoting glutamate Effects of receptor or postreceptor kinase phosphorylation on nociceptive stimuli of ARC neurons in normal rats and CFA inflammatory rats. Results the frequency of spontaneous discharge of ARC neurons in 1: 1 was significantly higher in inflammatory rats than that in normal rats, and the responses to nociceptive stimuli in the neurons were significantly higher in the inflammatory rats than in the normal rats. Intraventricular microinjection of MK-801 / 20nmol (Ro25-6981nmol / 6nmol) inhibited the response of ARC pain-specific neurons to nociceptive stimuli in normal and inflammatory rats. The microinjection of PP25nmol-GF109203Xnmol in the lateral ventricle could inhibit inflammation and inflammation in normal and inflammatory rats. Response of ARC pain specific neurons to nociceptive stimuli in rats. Conclusion (1) the excitability and the response to nociceptive stimulation of CFA neurons increased during peripheral CFA inflammation. The central NMDA receptors and their NR2B subunits were also increased. The response of ARC neurons to nociceptive stimuli in normal rats and CFA inflammatory rats.) Src protein tyrosine kinase and protein kinase C in brain may be involved in ARC pain specific neurons in normal rats and CFA inflammatory rats. The response of noxious stimuli is that ARC serves as a high center for the regulation of pain sensation at the level above the spinal cord. Peripheral inflammation can also produce central sensitization.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R364.5

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