【摘要】：目的甘丙肽受體1(galanin receptor 1,GALR1)信號通路在痛覺調(diào)節(jié)中發(fā)揮重要作用,該研究利用坐骨神經(jīng)慢性壓迫(chronic constriction injury of the sciatic nerve,CCI)大鼠模型,探索慢病毒介導(dǎo)的DREAM沉默治療在CCI模型大鼠疼痛中的作用及其對GALR1的表達(dá)調(diào)控。方法選擇健康雄性SD大鼠24只,隨機(jī)分為4組(n=6):即RNA干擾組、空白載體組、單純CCI組和正常對照組。鞘內(nèi)置管前后分別測定基礎(chǔ)痛閾,RNA干擾組和空白載體組于CCI后經(jīng)微導(dǎo)管給予pKCSHR-Puro/GFP-DREAM慢病毒和空白載體,并測定腰段脊髓內(nèi)下游調(diào)控元件拮抗分子(downstream regulatory element antagonist,DREAM)和GALR1的蛋白表達(dá)。結(jié)果大鼠痛閾的變化:手術(shù)同側(cè)熱痛閾和機(jī)械痛閾測定結(jié)果表明,CCI處理后,RNA干擾組、空白載體組及單純CCI組在各個(gè)時(shí)間點(diǎn)熱痛閾和機(jī)械痛閾較正常對照組均顯著降低(P0.01);RNA干擾組鞘內(nèi)注射后較注射前痛閾顯著升高,治療后相同時(shí)間點(diǎn)RNA干擾組較空白載體組及單純CCI組痛閾亦顯著升高。Western blotting結(jié)果表明,與其他實(shí)驗(yàn)組對比,RNA干擾組的DREAM蛋白表達(dá)水平顯著下調(diào),而GALR1蛋白表達(dá)水平較空白載體組、單純CCI組亦有顯著下調(diào)。結(jié)論 DREAM可以調(diào)控GALR1的表達(dá),提示甘丙肽受體1信號通路參與DREAM基因調(diào)節(jié)大鼠神經(jīng)病理性疼痛。
[Abstract]:Objective to study the effect of glycine receptor 1 (galanin receptor 1 (GALR1) signal pathway on the regulation of pain in rat model of chronic compression of sciatic nerve (chronic constriction injury of the sciatic nerve,CCI). To explore the role of lentivirus-mediated DREAM silencing in pain in CCI model rats and the regulation of GALR1 expression. Methods 24 healthy male SD rats were randomly divided into 4 groups: RNA interference group, blank vector group, simple CCI group and normal control group. The basal pain threshold was measured before and after intrathecal catheterization. The RNA interference group and blank carrier group were treated with pKCSHR-Puro/GFP-DREAM lentivirus and blank vector via microcatheter after CCI, and the antagonist molecule (downstream regulatory element antagonist, of the downstream regulatory element in the lumbar spinal cord was measured. DREAM) and GALR1 protein expression. Results the changes of pain threshold in rats: the results of ipsilateral thermal pain threshold and mechanical pain threshold measurement showed that after CCI treatment, RNA interference group, The thermal pain threshold and mechanical pain threshold of blank carrier group and simple CCI group were significantly lower than those of normal control group at each time point (P0.01). The pain threshold of RNA interference group was significantly higher than that of pre-injection group, and the pain threshold of RNA interference group was significantly higher than that of blank carrier group and CCI group at the same time after treatment. The results showed that the pain threshold of RNA interference group was significantly higher than that of other experimental groups. The expression level of DREAM protein in RNA interference group was significantly down-regulated, while GALR1 protein expression level was significantly lower than that in blank vector group and CCI alone group. Conclusion DREAM can regulate the expression of GALR1, suggesting that glycidyl receptor 1 signaling pathway is involved in the regulation of neuropathic pain by DREAM gene in rats.
【作者單位】： 湖南省人民醫(yī)院麻醉科;中南大學(xué)湘雅醫(yī)院麻醉科;
【基金】：國家自然科學(xué)基金(No:30872427) 湖南省自然科學(xué)基金(No:05JJ40136) 湖南省科技計(jì)劃資助項(xiàng)目(No:2012SK3241)
【分類號】：R-332

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本文編號：2398237