MrgC受体对大鼠骨癌痛的调制作用

发布时间：2018-03-08 21:34

本文选题：骨癌痛　切入点：MrgC受体　出处：《福建师范大学》2015年硕士论文　论文类型：学位论文

【摘要】：Mrg (Mas-related gene receptors),是G蛋白偶联受体家族的成员之一,它的mRNA仅特异性地存在于三叉神经节(trigeminal ganglia, TG)和背根神经节(dorsal root ganglion, DRG)的小型神经元细胞内。牛肾上腺髓质素8-22 (bovine adrenal medulla, BAM8-22)是内源性阿片肽家族成员BAM22的降解产物,是MrgC受体的特异性激动剂。鞘内应用BAM8-22激活MrgC受体具有抑制炎性痛大鼠痛觉过敏的作用。星形胶质细胞的活化与骨癌痛的维持过程有关,激活的星形胶质细胞和免疫细胞会释放炎性因子IL-1β,以及CGRP、nNOS等可能参与骨癌痛的维持过程。本实验应用伤害性热刺激、机械刺激引起的反应,以及影像学等方法鉴定骨癌痛模型的建立,并以骨癌痛模型为对象,运用行为学、荧光免疫组织化学染色等实验技术研究：(1)鞘内注射BAM8-22对骨癌痛诱发的机械痛觉超敏的影响；(2)鞘内注射BAM8-22对骨癌痛大鼠脊髓背角GFAP表达的影响；(3)鞘内注射BAM8-22对骨癌痛大鼠DRG中IL-1β、CGRP口nNOS阳性神经元表达的影响。结果显示：(1)利用Walker 256乳腺肉瘤细胞成功地建立了大鼠胫骨癌痛模型,骨癌鼠产生明显的热痛觉过敏和机械痛觉超敏；(2)骨癌痛大鼠在术后第6天出现机械痛觉超敏,到第16天左右最为明显,并得以维持。鞘内注射BAM8-22激活MrgC受体能即刻显著升高大鼠机械缩足阈值,持续约80min,还能明显延长机械基础阈值；(3)骨癌痛能够引起脊髓背角星形胶质细胞GFAP的表达明显增加,且胞体表现出肥大增生,突起增多；而鞘内注射BAM8-22能显著性地降低脊髓GFAP的表达。(4)骨癌痛大鼠DRG神经元中IL-1β、CGRP和nNOS阳性神经元的表达量增多,鞘内注射BAM8-22激活MrgC受体能够显著性地降低DRG中IL-1β、CGRP和nNOS的表达量。以上实验结果表明,激活MrgC受体对骨癌痛大鼠具有抗痛觉超敏作用,并能发挥抗伤害效应。这一机制可能是通过抑制脊髓星形胶质细胞的激活,以及通过抑制DRG中IL-1β、CG RPnNOS的表达来减弱骨癌痛诱发的痛觉超敏症状的。
[Abstract]:Mrg Mas-related gene receptor, a member of the G-protein-coupled receptor family, Its mRNA exists only in the small neurons of trigeminal ganglia (TGs) and dorsal root ganglia (DRGs). Bovine adrenomedullin 8-22 adrenal adrenal medulla (BAM8-22) is the degradation product of BAM22, a member of the endogenous opioid peptide family. It is a specific agonist of MrgC receptor. Intrathecal application of BAM8-22 to activate MrgC receptor can inhibit hyperalgesia in inflammatory pain rats. The activation of astrocytes is related to the maintenance process of bone cancer pain. Activated astrocytes and immune cells release inflammatory factor IL-1 尾, as well as CGRPnNOS, which may be involved in the maintenance of bone cancer pain. And imaging methods to identify the establishment of bone cancer pain model, and take the bone cancer pain model as the object, using behavior, Effects of intrathecal injection of BAM8-22 on mechanical hyperalgesia induced by pain in bone cancer: effect of intrathecal injection of BAM8-22 on GFAP expression in spinal dorsal horn of rats with bone cancer pain. The effect of nNOS positive neurons on the expression of IL-1 尾 CGRP-positive neurons in DRG of pain rats. The results showed that the rat tibial cancer pain model was successfully established by using Walker 256 breast sarcoma cells. Bone cancer rats developed obvious hyperthermia and mechanical hyperalgesia (2) Mechanical hyperalgesia occurred on the 6th day after operation in the rats with bone cancer, and was most obvious on the 16th day after operation. Intrathecal injection of BAM8-22 activated MrgC receptor increased the threshold of mechanical contraction in rats for about 80 min, and prolonged the threshold of mechanical basis for 80 min. The pain of bone cancer caused a significant increase in the expression of GFAP in astrocytes of the dorsal horn of spinal cord. However, intrathecal injection of BAM8-22 could significantly reduce the expression of GFAP in spinal cord in rats with pain of bone cancer, and increase the expression of IL-1 尾 -CGRP and nNOS positive neurons in DRG neurons of rats with pain of bone cancer, and the expression of IL-1 尾 -CGRP and nNOS in DRG neurons was significantly decreased by intrathecal injection of BAM8-22. Intrathecal injection of BAM8-22 to activate MrgC receptor could significantly reduce the expression of IL-1 尾 -CGRP and nNOS in DRG. The mechanism may be by inhibiting the activation of astrocytes in the spinal cord and the expression of IL-1 尾 -CG RPnNOS in DRG to attenuate the pain induced hyperalgesia of bone cancer.
【学位授予单位】：福建师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R738

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