多塞平对神经病理性痛大鼠脊髓p38MAPK表达的影响  

Effect of doxepin on expression of p38MAPK in spinal cord of rats with neuropathic pain

作　　者：楚云超 刘敬平 葛维鹏[1] 杜梅青[1] 郑观荣[1] 车磊 黄科昌[3] 王中伟[1] Chu Yunchao;Liu Jingping;Ge Weipeng;Du Meiqing;Zheng Guanrong;Che Lei;Huang Kechang;Wang Zhongwei(Department of Pain,Shengli Oilfield Central Hospital,Dongying 257034,Shandong Province,China;Department of Anesthesiology,Linyi People's Hospital,Linyi 276000,Chin;Department of Pain,Affiliated Hospital of Weifang Medical University,Weifang 261031,China)

机构地区：[1]胜利油田中心医院疼痛科,东营市257034 [2]临沂市人民医院麻醉科,276000 [3]潍坊医学院附属医院疼痛科,261031

出　　处：《中华麻醉学杂志》2018年第12期1467-1470,共4页Chinese Journal of Anesthesiology

基　　金：山东省医药卫生科技发展计划项目(2013WS0283).

摘　　要：目的评价多塞平对神经病理性痛大鼠脊髓p38丝裂原活化蛋白酶(p38MAPK)表达的影响。方法取鞘内置管成功的清洁级雄性Wistar大鼠60只,体重200~250,采用随机数字表法分为3组(n=20):假手术组(S组)、神经病理性痛组(NP组)和多塞平组(D组)。采用坐骨神经慢性压迫(CCI)法制备神经病理性痛模型。D组于CCI后3、7、14和21d时鞘内注射20mmol/L多塞平10μl。于CCI前1d(T0)、CCI后3、7、14和21d(T1-4)时测定机械缩足反应阈(MWT)和热缩足潜伏期(TWL)。T4痛阈测定结束后处死大鼠,取脊髓L4-6节段,采用Westernblot法测定脊髓p38MAPK的表达。结果与S组比较,NP组和D组T2-4时MWT降低,TWL缩短,脊髓p38MAPK表达上调(P<0.05);与NP组比较,D组T2-4时MWT升高,TWL延长,脊髓p38MAPK表达下调(P<0.05)。结论多塞平减轻大鼠神经病理性痛的机制可能与脊髓p38MAPK表达下调有关。Objective To evaluate the effect of doxepin on the expression of p38 mitogen-activated protein kinase(p38 MAPK) in the spinal cord of rats with neuropathic pain(NP). Methods Sixty clean-grade male Wistar rats in which intrathecal catheters were successfully implanted, weighing 200-250 g, were divided into 3 groups(n=20 each) by a random number table method: sham operation group(S group), NP group and doxepin group(D group). NP was induced by chronic constriction injury(CCI) to sciatic nerve. Doxepin 20 mmol/L(10 μl) was intrathecally injected at 3, 7, 14 and 21 days after CCI(T1-4) in group D. The mechanical paw withdrawal threshold(MWT) and thermal paw withdrawal latency(TWL) were measured at 1 day before CCI(T0) and at T1-4. The rats were sacrificed after measurement of pain threshold at T4, and L4-6 segments of the spinal cord were removed for determination of the expression of p38MAPK protein by Western blot. Results Compared with S group, MWT was significantly decreased and TWL was shortened at T2-4, and the expression of p38MAPK protein was up-regulated in NP and D groups(P<0.05). Compared with NP group, MWT was significantly increased and TWL was prolonged at T2-4, and the expression of p38MAPK protein was down-regulated in D group(P<0.05). Conclusion The mechanism by which doxepin mitigates NP is related to down-regulating p38MAPK expression in the spinal cord of rats.

关 键 词：多塞平 神经痛 P38丝裂原活化蛋白激酶类 脊髓 

分 类 号：R965[医药卫生—药理学]