本文選題：骨癌痛　切入點(diǎn)：MrgC受體　出處：《福建師范大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：Mrg (Mas-related gene receptors),是G蛋白偶聯(lián)受體家族的成員之一,它的mRNA僅特異性地存在于三叉神經(jīng)節(jié)(trigeminal ganglia, TG)和背根神經(jīng)節(jié)(dorsal root ganglion, DRG)的小型神經(jīng)元細(xì)胞內(nèi)。牛腎上腺髓質(zhì)素8-22 (bovine adrenal medulla, BAM8-22)是內(nèi)源性阿片肽家族成員BAM22的降解產(chǎn)物,是MrgC受體的特異性激動劑。鞘內(nèi)應(yīng)用BAM8-22激活MrgC受體具有抑制炎性痛大鼠痛覺過敏的作用。星形膠質(zhì)細(xì)胞的活化與骨癌痛的維持過程有關(guān),激活的星形膠質(zhì)細(xì)胞和免疫細(xì)胞會釋放炎性因子IL-1β,以及CGRP、nNOS等可能參與骨癌痛的維持過程。本實(shí)驗(yàn)應(yīng)用傷害性熱刺激、機(jī)械刺激引起的反應(yīng),以及影像學(xué)等方法鑒定骨癌痛模型的建立,并以骨癌痛模型為對象,運(yùn)用行為學(xué)、熒光免疫組織化學(xué)染色等實(shí)驗(yàn)技術(shù)研究：(1)鞘內(nèi)注射BAM8-22對骨癌痛誘發(fā)的機(jī)械痛覺超敏的影響；(2)鞘內(nèi)注射BAM8-22對骨癌痛大鼠脊髓背角GFAP表達(dá)的影響；(3)鞘內(nèi)注射BAM8-22對骨癌痛大鼠DRG中IL-1β、CGRP口nNOS陽性神經(jīng)元表達(dá)的影響。結(jié)果顯示：(1)利用Walker 256乳腺肉瘤細(xì)胞成功地建立了大鼠脛骨癌痛模型,骨癌鼠產(chǎn)生明顯的熱痛覺過敏和機(jī)械痛覺超敏；(2)骨癌痛大鼠在術(shù)后第6天出現(xiàn)機(jī)械痛覺超敏,到第16天左右最為明顯,并得以維持。鞘內(nèi)注射BAM8-22激活MrgC受體能即刻顯著升高大鼠機(jī)械縮足閾值,持續(xù)約80min,還能明顯延長機(jī)械基礎(chǔ)閾值；(3)骨癌痛能夠引起脊髓背角星形膠質(zhì)細(xì)胞GFAP的表達(dá)明顯增加,且胞體表現(xiàn)出肥大增生,突起增多；而鞘內(nèi)注射BAM8-22能顯著性地降低脊髓GFAP的表達(dá)。(4)骨癌痛大鼠DRG神經(jīng)元中IL-1β、CGRP和nNOS陽性神經(jīng)元的表達(dá)量增多,鞘內(nèi)注射BAM8-22激活MrgC受體能夠顯著性地降低DRG中IL-1β、CGRP和nNOS的表達(dá)量。以上實(shí)驗(yàn)結(jié)果表明,激活MrgC受體對骨癌痛大鼠具有抗痛覺超敏作用,并能發(fā)揮抗傷害效應(yīng)。這一機(jī)制可能是通過抑制脊髓星形膠質(zhì)細(xì)胞的激活,以及通過抑制DRG中IL-1β、CG RPnNOS的表達(dá)來減弱骨癌痛誘發(fā)的痛覺超敏癥狀的。
[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.
【學(xué)位授予單位】：福建師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R738

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相關(guān)期刊論文 前1條

1 孫濤;宋文閣;姚尚龍;傅志儉;;神經(jīng)病理性疼痛大鼠脊髓星形膠質(zhì)細(xì)胞增殖活化的變化[J];中華麻醉學(xué)雜志;2006年09期

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本文編號：1585668