非NMDA型兴奋性氨基酸受体促进大鼠伤害性传入引起的脊髓后角星形胶质细胞的激活

发布时间：2018-06-05 01:35

本文选题：炎性痛及痛过敏 + 蜜蜂毒　；参考：《河北医科大学》2005年硕士论文

【摘要】：传统观点认为神经元是神经系统的基本功能单位,中枢神经系统对伤害性刺激的感受、传导以及调节,都是由神经元介导的。但近年来研究表明,脊髓胶质细胞在病理性痛的产生和维持中发挥重要作用。很多伤害性刺激,如皮下炎性刺激、外周神经损伤等均可以激活脊髓后角胶质细胞。给予胶质细胞抑制剂(如氟代柠檬酸、CNI-1493)可明显抑制伤害性刺激引起的热痛敏和机械性痛敏。体外实验表明胶质细胞可以被一些疼痛相关物质,如ATP、兴奋性氨基酸(excitatoryamino acids ,EAAs)、前列腺素、P 物质、一氧化氮等激活。激活的脊髓胶质细胞可以产生许多细胞因子和神经活性物质促进伤害性信息的传递。由此可见脊髓胶质细胞的激活在伤害性信息处理过程中发挥重要作用。但伤害性传入引起脊髓胶质细胞激活的机制有待阐明。 EAAs 是脊髓中介导伤害性信息传递的重要神经递质,可通过N-甲基-D-天门冬氨酸(N-methyl-D-asparte,NMDA )和非NMDA受体介导伤害性信息,其中NMDA受体除介导脊髓后角痛相关神经元的兴奋外,在伤害性传入引起的脊髓后角星形胶质细胞的激活中也发挥重要作用,但非NMDA 受体是否参与伤害性传入引起的脊髓后角星形胶质细胞的激活尚未见报道。因此,本实验通过观察非NMDA 受体拮抗剂6-cyano-7- nitroquinoxaline-2,3-dione(CNQX)对大鼠蜜蜂毒(Bee venom,BV)炎性痛及痛过敏所致脊髓后角星形胶质细胞胶质原纤酸性蛋白(glial fibrillary acidic protein,GFAP)表达的影响,以及非NMDA 受体激动剂海人藻酸(kainic acid,KA)在引起伤害性感受过程中对脊髓后角星形胶质细胞GFAP 表达的影响,探讨非NMDA 受体在伤害性信息传入所致脊髓后角星型胶质细胞激活中的作用。 1 非NMDA 受体拮抗剂CNQX 对大鼠蜂毒炎性痛及痛过敏所致脊髓后角星形胶质细胞GFAP 表达的影响雄性Sprague-Dawley 大鼠77 只,体重270-280g。动物随机分为4 组,分别为对照(Control)组、蜂毒(BV)组、BV +溶剂二甲基亚砜(DMSO)对照组、BV+CNQX 组。其中BV+CNQX 组根据CNQX 剂量分为2.5nmol、10nmol、 40nmol三个亚组。对照组足底皮下注射生理盐水(NS)50μl,其余各组均于右后足底皮下注射BV 溶液50μl(4g·L-1)致外周炎性痛及痛过敏。BV+DMSO 组、BV+CNQX 组于足底注射蜂毒前15min 鞘内注射10μl 溶剂(50% DMSO)或CNQX溶液。各组均于足底注射后1h 或24h 取材,免疫组化法观察脊髓后角GFAP 表达的变化。取材前测定自发缩足反射次数(1h),并应用温水浴法和热辐射法测定热甩尾潜伏期(24h)。结果发现,①缩足反射足底注射蜂毒后大鼠出现缩足反射。鞘内给予DMSO 对上述BV 注射引起的缩足反射次数无显著影响(P0.05),而鞘内给予CNQX 则可使大鼠的退缩反射次数显著降低(P0.05),且降低的程度与CNQX剂量显示明显的剂量依赖性。②热甩尾潜伏期大鼠右后足掌面皮下注射蜂毒后其热甩尾潜伏期显著缩短(P0.05)。
[Abstract]:The traditional view is that neurons are the basic functional units of the nervous system. The sensory, conduction and regulation of the central nervous system are mediated by neurons. However, in recent years, studies have shown that the spinal glia cells play an important role in the production and maintenance of pathological pain. Many nociceptive stimuli, such as subcutaneous inflammatory stimuli, are important. Peripheral nerve injury, such as peripheral nerve injury, can activate glial cells in the posterior horn of the spinal cord. Glial cell inhibitors (such as fluorocitric acid, CNI-1493) can obviously inhibit the thermal pain sensitivity and mechanical sensitization induced by nociceptive stimuli. In vitro experiments show that glial cells can be treated with some pain related substances, such as ATP, excitatoryamino acids, EA. As) activation of prostaglandins, substance P, nitric oxide. Activated spinal glial cells can produce many cytokines and neuroactive substances that promote the transmission of noxious information. Thus, the activation of spinal glial cells plays an important role in the process of noxious information processing. The mechanism remains to be clarified.
EAAs is an important neurotransmitter for the transmission of nociceptive information in the spinal cord, which mediates nociceptive information through the N- methyl -D- aspartate (N-methyl-D-asparte, NMDA) and non NMDA receptors, in which the NMDA receptor activates the astrocytes in the posterior horn of the spinal cord caused by nociceptive afferent in addition to the excitation of the spinal cord hornpain related neurons. It also plays an important role. However, whether the non NMDA receptor participates in the activation of astrocytes in spinal dorsal horn induced by noxious afferent has not been reported.
Therefore, we observed the non NMDA receptor antagonist 6-cyano-7-.
The effect of nitroquinoxaline-2,3-dione (CNQX) on the expression of glial fibrillary acidic protein (glial fibrillary acidic protein, GFAP) of astrocytes in the posterior horn of the spinal cord caused by Bee venom (BV) and pain allergy, and the non NMDA receptor agonist, sea human alginic acid (kainic), in the process of causing injury to the spinal cord in the spinal cord The effect of non NMDA receptor on the activation of astrocytes in spinal dorsal horn induced by noxious information was explored by GFAP expression in the posterior horn astrocytes.
1 Effect of non NMDA receptor antagonist CNQX on GFAP expression in astrocytes of spinal dorsal horn in rats with bee venom inflammatory pain and hyperalgesia
77 male Sprague-Dawley rats and weight 270-280g. animals were randomly divided into 4 groups: control (Control) group, bee venom (BV) group, BV + solvent two methyl sulfoxide (DMSO) control group, BV+CNQX group. The BV+CNQX group was divided into 2.5nmol, 10nmol, 40nmol three subgroups according to the CNQX dosage. The control group subcutaneous injection of saline 50 um, the rest All groups were subcutaneously injected into the right posterior foot by subcutaneous injection of BV solution 50 u l (4G. L-1) to peripheral inflammatory pain and hyperalgesia in.BV+DMSO group. Group BV+CNQX was injected with 10 u l solvent (50% DMSO) or CNQX solution in the 15min sheath before injection of bee venom in the foot. All groups were taken after the plantar injection 1H or 24h, the changes of the posterior horn of the spinal cord were observed by immunohistochemical method. The number of spontaneous retraction reflex (1H) was measured, and the thermal flick latency (24h) was measured by warm water bath and thermal radiation.
The results showed that the contraction foot reflex was found in the rats after the foot injection of the foot, and the intrathecal administration of DMSO had no significant effect on the times of the reflexes caused by the BV injection (P0.05), while the intrathecal CNQX could significantly reduce the number of retraction reflex (P0.05) in the rats (P0.05), and the degree of reduction was significantly dependent on the dose of CNQX. (2) the latent period of heat tail flick was significantly shortened (P0.05) after the injection of bee venom from the right posterior foot palmar skin in the thermal tail flick incubation period.
【学位授予单位】：河北医科大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R363

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