摘要目的 评价右美托咪啶对神经病理性痛大鼠脊髓嘌呤受体P2X4(P2XR)mRNA和p38丝裂原活化蛋白激酶(p38 MAPK)mRNA表达的影响.方法 雄性SD大鼠72只,体重180～220 g,采用随机数字表法,将大鼠随机分为3组(n=24):假手术组(S组)、神经病理性痛组(NP组)和右美托咪啶组( DEX组).采用坐骨神经慢性压迫性损伤法建立神经病理性痛模型.DEX组于术后即刻开始每天腹腔注射右美托咪啶50 μg/kg,S组和NP组腹腔注射等容量生理盐水.于术前1d、术后1、3、7和14 d时测定机械痛阈(MWT)和热痛阈(TWL).术后测定痛阈后随机取6只大鼠,断头处死,取损伤侧L4～6脊髓组织,采用RT-PCR法测定P2X4R mRNA和p38 MAPK mRNA表达.结果 与S组比较,NP组和DEX组术后MWT及TWL降低,脊髓P2X4R mRNA和p38 MAPK mRNA表达上调(P＜0.05).与NP组比较,DE组术后MWT及TWL升高,脊髓P2X4R mRNA和p38 MAPK mRNA表达下调(P＜0.05).与术后7d时比较,NP组和DEX组于术后1、3、14 d时MWT和TWL升高,P2X4R mRNA和p38MAPK mRNA表达下调(P＜0.05).结论 右美托咪啶减轻大鼠神经病理性痛的机制与抑制P2X4RmRNA和p38 MAPK mRNA的表达有关.

abstractsObjective To investigate the effect of dexmedetomidine on the expression of purinergic P2X4 receptor (P2X4R) mRNA and p38 mitogen-activated protein kinase (p38 MAPK) mRNA in spinal cord in a rat model of neuropathic pain (NP).Methods Seventy-two male SD rats weighing 180-220 g were randomly assigned into 3 groups ( n =24 each):sham operation group (group S),group NP and dexmedetomidine group ( group DEX).The animals were anesthetized with intraperitoneal 10％ choral hydrate 350 mg/kg.NP was induced by chronic constrictive injury (CCI).The right sciatic nerve was exposed and 4 ligatures were placed on sciatic nerve at 1 mm intervals with 4-0 silk thread in groups NP and DEX.In group S,the right sciatic nerve was only exposed but not ligated.Dexmedetomidine 50μg/kg was injected intraperitoneally daily staring from the end of operation,while the equal volume of normal saline was injected in groups S and NT.The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured on day 1 before operation and on day 1,3,7 and 14 after operation.Six animals were sacrificed after MWT and TWL measurement on day 1,3,7 and 14 after operation in each group,the L4～6 segment of spinal cords was removed for determination of P2X4 R mRNA and p38 MAPK mRNA expression by RT-PCR.Results Compared with group S,MWT and TWL were significantly decreased and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly up-regulated after operation in groups NP and DEX ( P ＜0.05).Compared with group NP,TWL and MWT were significantly increased and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly down-regulated after operation in group DEX ( P ＜ 0.05 ).TWL and MWT were significantly higher and the expression of P2X4 R mRNA and p38 MAPK mRNA was significantly lower on day 1,3 and 14 after operation than on day 7 after operation in groups NiP and DEX ( P ＜ 0.05).Conclusion The mechanism by which dexmedetomidine attenuates NP is related to inhibition of the expression of P2X4 R mRNA and p38 MAPK in rats.