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鞘内注射右旋美托咪啶对正常大鼠的镇痛效果及对脊髓背角c-fos蛋白表达的影响 被引量:2

The effects of intrathecal injection with dexmedetomidine on analgesia and c-fos expression in lumbar spinal cord dorsal horn in rats
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摘要 目的研究髓鞘内注射右旋美托咪啶(Dex)对大鼠的镇痛作用以及对于大鼠脊髓背角的c-fos蛋白表达的影响。方法选择60只SD雄性大鼠,分为五个组,每个组12只:正常对照组(不进行任何的处理)、生理盐水组(生理盐水10μl)以及髓鞘内注射给药组0.75μg/kg Dex 10μl组(Dex1组)、1.50μg/kg Dex 10μl(Dex2组)、3.00μg/kg Dex 10μl(Dex3组)。于给药前、给药后30 min观察大鼠机械缩足阈值(PWMT)的变化和给药前、给药后1 h观察大鼠甩尾潜伏期(TFL)的变化,计算最大抗伤害效应比率(%MPE)。取给药后7 h、24 h、48 h的脊髓腰膨大处,检测Fos蛋白免疫反应阳性(FLI)水平。结果 PWMT的结果:给药30 min与给药前相比,Dex1组、Dex2组和Dex3组各组的机械缩足阈值升高(P<0.05);给药后,Dex1组、Dex2组和Dex3组的PWMT较正常对照组和生理盐水组明显增高(P<0.05);Dex3组的PWMT比Dex1组和Dex2组高(P<0.05)。TFL的结果:给药30 min与给药前相比,Dex1组、Dex2组和Dex3组的TFL呈现出明显升高的趋势(P<0.05);给药后,Dex1组、Dex2组和Dex3组的TFL较正常对照组和生理盐水组的表达水平明显增高(P<0.05);Dex3组的TFL比Dex1组和Dex2组的高(P<0.05)。%MPE的结果:Dex1、Dex2和Dex3组的%MPE比对照组和生理盐水组的高(P<0.05);Dex3组的%MPE要远远高于Dex1组和Dex2组(P<0.05)。脊髓背角FLI表达水平:给药后7 h时,Dex3组的FLI表达水平比正常对照组和生理盐水组的表达强(P<0.05);给药后24 h时,Dex3组的比正常对照组、生理盐水组、Dex1组和Dex2组的表达水平高(P<0.05);给后48 h时,各组之间无统计学差异。结论髓鞘内注射右旋美托咪啶,能够对大鼠产生一定的镇静作用,并且对于脊髓神经不会产生损伤;髓鞘内部应该小剂量的注射右旋美托咪啶,大剂量3.00μg/kg时虽然镇痛效果较强,但存在短暂的可逆性的脊髓神经毒性。 Objective To investigate the effects of intrathecal injection with dexmedetomidine on analgesia and c - fos expression in lum-bar spinal cord dorsal horn in rats. Methods Sixty male SD rats were randomly divided into 5 groups as follows (n = 12 each):control group (normal rats did not received any intervention),other groups were intrathecal injected:saline group (normal saline 10 μl),Dex1 group (0. 75μg/ kg Dex 10 μl),Dex2 group (1. 50 μg/ kg Dex 10 μl)and Dex3 group (3. 00 μg/ kg Dex 10 μl). To assess the level of paw withdrawal me-chanical threshold (PWMT)at baseline and 30 min after injection and the level of thermal tail flick latency (TFL)at baseline and 1 h after injec-tion,calculate the percentage of the maximum possible effect (% MPE). Expression of c - fos in lumbar spinal cord was assessed by immunohisto-chemical analysis at 7 h,24 h and 48 h after injection. Results The levels of PWMT in Dex3 were higher than Dex1 and Dex2. While Levels of TFL were increased significantly (P 〈 0. 05)after injection with Dex1,Dex2 and Dex3. The levels of TFL in Dex1,Dex2 and Dex3 groups were higher than control and saline groups after injection (P 〈 0. 05). The levels of TFL in Dex3 were higher than Dex1 and Dex2. % MPE of Dex1, Dex2 and Dex3 were more than control and saline (P 〈 0. 05),and Dex3 was still more than Dex1 and Dex2 in % MPE (P 〈 0. 05). Expres-sion of c - fos was higher in Dex3 than in other groups at 24 h after injection (P 〈 0. 05),which was also higher in Dex3 group than control and saline group (P 〈 0. 05)at 7 h after injection. Levels of PWMT were increased significantly (P 〈 0. 05)after injection with Dex1,Dex2 and Dex3. The levels of PWMT in Dex1,Dex2 and Dex3 groups were higher than control and saline groups after injection (P 〈 0. 05). Conclusion There are antinociceptive effect and non - neurotoxicity after low dose of intrathecal injection with dexmedetomidine 0. 75 μg/ kg and 1. 50 μg/kg,while high dose of 3. 00 μg/ kg dexmedetomidine associates with transiently reversible neurotoxicity with satisfactory antinociceptive effect.
出处 《临床和实验医学杂志》 2018年第1期4-9,共6页 Journal of Clinical and Experimental Medicine
基金 深圳市科学计划局科技计划项目(编号:201406093001150)
关键词 大鼠 右旋美托咪啶 镇痛 药物毒性 脊髓 Rats Dexmedetomidine analgesia drug toxicity spinal
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