右美托咪定对病理性神经痛坐骨神经卡压性模型大鼠镇痛作用的影响  

The analgesic effect of dextromethazine via the P38MARK signaling pathway on pathologic neuropathic sciatic compression model rats

作　　者：韩梅 赵昭[1] 冯军 HAN Mei;ZHAO Zhao;FENG Jun(Department of Anesthesiology, Shenzhen Second People′s Hospital, Shenzhen 518035, China)

机构地区：[1]深圳市第二人民医院麻醉科,深圳518035

出　　处：《新疆医科大学学报》2019年第5期619-623,共5页Journal of Xinjiang Medical University

基　　金：深圳市科技计划项目(JCYJ20150331091533450)

摘　　要：目的探讨右美托咪定对病理性神经痛坐骨神经卡压性模型大鼠镇痛作用的影响。方法选择雄性SD大鼠36只,体重为220～265 g,随机分为3组(对照组、病理性神经痛模型组、右美托咪定组),每组各12只。对照组大鼠进行假手术处理,切开肌层并进行坐骨神经分离。病理性神经痛模型组大鼠进行坐骨神经结扎,制作病理性坐骨卡压性损伤模型,每天向鞘内注射2μg/kg的生理盐水,共注射14 d;右美托咪定组大鼠进行坐骨神经结扎,制作病理性坐骨卡压性损伤模型,每天向鞘内注射2μg/kg的右美托咪定。观察各组大鼠热缩足反射潜伏期、机械缩足反射潜伏期,并用免疫组织化学法测定脊髓背根神经节P38丝裂原活化蛋白激酶(P38MAPK)表达情况,采用反转录聚合酶链式反应检测P38MAPKA mRNA表达水平。结果与对照组比较,病理性神经痛模型组与右美托咪定组大鼠损伤同侧脚趾并拢或内收,伴随或不伴随自发性甩腿、舔足、踮地行走等疼痛表现均有所减少。在给药后第3天,右美托咪定组热缩足反射潜伏期明显长于病理性神经痛模型组(P<0.05);在给药后第3天,右美托咪定组机械缩足反射潜伏期明显长于病理性神经痛模型组(P<0.05);病理性神经痛模型组与右美托咪定组P38MAPK平均光密度明显高于对照组(P<0.05),而右美托咪定组明显低于病理性神经痛模型组(P<0.05);病理性神经痛模型组与右美托咪定组P38MAPK mRNA水平明显高于对照组(P<0.05),而右美托咪定组与病理性神经痛模型组相比,术后1 d无明显差异(P>0.05),但随着时间推移P38MAPK mRNA表达水平明显降低(P<0.05)。结论对病理性神经痛大鼠进行鞘内注射右美托咪定可缩短大鼠热缩足反射潜伏期和机械缩足反射潜伏期,其疼痛缓解作用的发挥可能是通过下调P38MAPK mRNA表达,从而抑制P38MAPK活化实现的。Objective To investigate the effect of dexmedetomidine on the analgesic effect of sciatic nerve compression model rats with pathological neuralgia. Methods 36 male Sprague-Dawley rats, weighing 220-265 g, were randomly divided into 3 groups(control group, pathological neuralgia model group, dexmedetomidine group), 12 in each group. The control group rats were subjected to sham operation, the muscle layer was cut and the sciatic nerve was separated. Rats in the pathological neuropathic model group were subjected to sciatic nerve ligation, and a pathological sciatic compression injury model was made. Intrathecal injection of 2 μg/kg of normal saline for 14 days;dexmedetomidine group of rats with sciatic nerve ligation, a pathological sciatic compression injury model was made, and 2 μg/kg of dexmedetomidine was injected intrathecally daily. The incubation period and mechanical contraction latency of heat-shrinking group were observed. The expression of P38 mitogen-activated protein kinase(P38 MAPK) in spinal dorsal root ganglia was determined by immunohistochemistry. The expression level of P38 MAPKA mRNA was detected by reverse transcription polymerase chain reaction. Results Compared with the control group, the injured toes were close together or adducted, and the clinical manifestations of pain with or without spontaneous lameness, and squatting were reduced in the pathological neuralgia model group and the dexmedetomidine group;on the third day after administration, the dexmedetomidine group was significantly longer than the model group(P<0.05). On the 3 rd day after administration, the mechanical contraction latency of dexmedetomidine group was significantly longer than that of pathological neuralgia model group(P<0.05);In pathological neuralgia model group and dexmedetomidine group,the average optical density of P38 MAPK was significantly higher than that of the control group(P<0.05), while the dexmedetomidine group was significantly lower than the pathological neuralgia model group(P<0.05). At the 1 st day

关 键 词：P38MARK信号通路 右美托咪定 病理性神经痛 坐骨神经卡压性模型 大鼠 镇痛 

分 类 号：R916.64[医药卫生—药学]