鞘内注射不同剂量右美托咪啶对大鼠的抗伤害效应和脊髓神经毒性

Analgesic effcacy and spinal neurotoxicity of intrathecal different doses of dexmedetomidine in rats

目的评价鞘内注射右美托咪啶对大鼠的抗伤害效应和脊髓神经毒性。方法雄性SD大鼠60只，体重180—220g，采用随机数字表法，将其随机分为5组（n=12）：对照组（C组）不做任何处理；生理盐水组（N组）鞘内注射生理盐水10m；不同剂量右美托咪啶组分别鞘内注射右美托眯啶0．75μg／kg组（D1组）、1．50μg／kg组（D2组）、3．00μg／kg组（眈组），均用生理盐水稀释至10μl。于鞘内给药前和给药后30min时测定机械缩足阈值（PWMT），于鞘内给药前和给药后60min时测定辐射热甩尾潜伏期（TFL），计算最大抗伤害效应（MPE）百分比。于给药后7、24和48h时，取L1-6。脊髓节段，观察病理学结果，并采用免疫组化法测定c—Fos蛋白表达水平。结果与C组和N组比较，D1组、D2组和D3组给药后30min时PWMT升高，给药后60min时TFL和MPE百分比升高（P〈0．05）；与D1组和耽组比较，现组给药后30min时PWMT升高，给药后60min时TFL和MPE百分比升高（P〈0．05）；D1组和现组PWMT、TFL和MPE百分比差异无统计学意义（P〉O．05）。与C组和N组比较，D1组和D2组给药后各时点脊髓背角c-Fos蛋白表达差异无统计学意义（P〉0．05），D3组给药后7和24h时脊髓背角c-Fos蛋白表达上调（P〈0．05），给药后48h时脊髓背角c—Fos蛋白表达差异无统计学意义（P〉0．05）；与D1组和D2组比较，功组给药后24h时脊髓背角c—Fos蛋白表达上调（P〈O．05）。n组给药后24h时可见脊髓轻度损伤。结论鞘内注射右美托咪啶对大鼠可产生抗伤害效应。鞘内注射3．00μg/kg右美托咪啶抗伤害效应最强，但可产生短暂的脊髓神经毒性。

ObJective To investigate the analgesic efficacy and spinal neurotoxicity of intrathecal （IT） different doses of dexmedetomidine in rats. Methods Sixty male SD rats weighing 180-220 g were randomly divided into 5 groups （ n = 12 each） ： groupnormal control （group C） ; group IT normal saline （group N） ; different doses of dexmedetomidine groups received IT dexmedetomidine 0.75, 1.50 and 3.00 μg/kg respectively （groups D1-3 ）. Paw withdrawal threshold to mechanical stimulation （PWMT） with van Frey filaments and tail flick latency （TFL） to a thermal nociceptive stimulus were measured before （To, baseline） and at 30 or 60 min after IT dexmedetomidine or normal saline administration （T1 , T2 ） and the percentage of the maximum possible effect （MPE） was calculated. Lumbar segment of the spinal cord （L4-6 ） was removed for microscopic examination and determination of e-Fos expression （by iramuno-histochernlstry） at 7, 24 and 48 h after IT dexmedetomidine or normal saline administration. Results PWMT, TFL and the percentage of MPE were significantly increased after IT dexmedetomidine as compared with the baseline values at To in groups D1-3 （ P 〈 0.05）. PWMT was significantly higher at T1 and TFL and the percentage of MPE were higher at T2 in groups D1-3 than in groups C and N, and in group D3 than in groups D1 ,2 （ P 〈 0.05）. At 7,24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in groups C and N（ P 〈 0.05）. There was no significant difference in c-Fos expression at 48 h af- ter IT dexmedetomidine between group D3 and groups C and N （ P 〉 0.05）. At 24 h after IT dexmedetomidine c-Fos protein expression was significantly higher in group D3 than in other 4 groups（ P ~ 0.05）. Slight spinal cord injury was observed at 24 h after IT dexmedetomidine in group D3 . Conclusion IT dexmedetomidine has antinoci- ceptive effect. High dose dexmedetomidine IT can produce transient reversible toxicity to the spinal cord.