中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2011年
6期
710-713
,共4页
侯家保%肖兴鹏%夏中元%赵博%吴洋
侯傢保%肖興鵬%夏中元%趙博%吳洋
후가보%초흥붕%하중원%조박%오양
右美托咪啶%注射,脊髓%镇痛%药物毒性
右美託咪啶%註射,脊髓%鎮痛%藥物毒性
우미탁미정%주사,척수%진통%약물독성
Dexmedetomidine%Injections,spinal%Analgesia%Drug toxicity
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180~220 g,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10 μl;不同剂量右美托咪啶组分别鞘内注射右美托咪啶0.75μg/kg组(D1组)、1.50μg/kg组(D2组)、3.00 μg/kg组(D3组),均用生理盐水稀释至10 μl.于鞘内给药前和给药后30 min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48 h时,取L4-6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D2组比较,D3组给药后30 min时PWMT升高,给药后60min时TFL和MPE百分比升高(P<0.05);D1组和D2组PWMT、TFL和MPE百分比差异无统计学意义(P>0.05).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24 h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,D3组给药后24 h时脊髓背角c-Fos蛋白表达上调(P<0.05).D3组给药后24 h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.
目的 評價鞘內註射右美託咪啶對大鼠的抗傷害效應和脊髓神經毒性.方法 雄性SD大鼠60隻,體重180~220 g,採用隨機數字錶法,將其隨機分為5組(n=12):對照組(C組)不做任何處理;生理鹽水組(N組)鞘內註射生理鹽水10 μl;不同劑量右美託咪啶組分彆鞘內註射右美託咪啶0.75μg/kg組(D1組)、1.50μg/kg組(D2組)、3.00 μg/kg組(D3組),均用生理鹽水稀釋至10 μl.于鞘內給藥前和給藥後30 min時測定機械縮足閾值(PWMT),于鞘內給藥前和給藥後60min時測定輻射熱甩尾潛伏期(TFL),計算最大抗傷害效應(MPE)百分比.于給藥後7、24和48 h時,取L4-6脊髓節段,觀察病理學結果,併採用免疫組化法測定c-Fos蛋白錶達水平.結果 與C組和N組比較,D1組、D2組和D3組給藥後30min時PWMT升高,給藥後60min時TFL和MPE百分比升高(P<0.05);與D1組和D2組比較,D3組給藥後30 min時PWMT升高,給藥後60min時TFL和MPE百分比升高(P<0.05);D1組和D2組PWMT、TFL和MPE百分比差異無統計學意義(P>0.05).與C組和N組比較,D1組和D2組給藥後各時點脊髓揹角c-Fos蛋白錶達差異無統計學意義(P>0.05),D3組給藥後7和24 h時脊髓揹角c-Fos蛋白錶達上調(P<0.05),給藥後48h時脊髓揹角c-Fos蛋白錶達差異無統計學意義(P>0.05);與D1組和D2組比較,D3組給藥後24 h時脊髓揹角c-Fos蛋白錶達上調(P<0.05).D3組給藥後24 h時可見脊髓輕度損傷.結論 鞘內註射右美託咪啶對大鼠可產生抗傷害效應.鞘內註射3.00μg/kg右美託咪啶抗傷害效應最彊,但可產生短暫的脊髓神經毒性.
목적 평개초내주사우미탁미정대대서적항상해효응화척수신경독성.방법 웅성SD대서60지,체중180~220 g,채용수궤수자표법,장기수궤분위5조(n=12):대조조(C조)불주임하처리;생리염수조(N조)초내주사생리염수10 μl;불동제량우미탁미정조분별초내주사우미탁미정0.75μg/kg조(D1조)、1.50μg/kg조(D2조)、3.00 μg/kg조(D3조),균용생리염수희석지10 μl.우초내급약전화급약후30 min시측정궤계축족역치(PWMT),우초내급약전화급약후60min시측정복사열솔미잠복기(TFL),계산최대항상해효응(MPE)백분비.우급약후7、24화48 h시,취L4-6척수절단,관찰병이학결과,병채용면역조화법측정c-Fos단백표체수평.결과 여C조화N조비교,D1조、D2조화D3조급약후30min시PWMT승고,급약후60min시TFL화MPE백분비승고(P<0.05);여D1조화D2조비교,D3조급약후30 min시PWMT승고,급약후60min시TFL화MPE백분비승고(P<0.05);D1조화D2조PWMT、TFL화MPE백분비차이무통계학의의(P>0.05).여C조화N조비교,D1조화D2조급약후각시점척수배각c-Fos단백표체차이무통계학의의(P>0.05),D3조급약후7화24 h시척수배각c-Fos단백표체상조(P<0.05),급약후48h시척수배각c-Fos단백표체차이무통계학의의(P>0.05);여D1조화D2조비교,D3조급약후24 h시척수배각c-Fos단백표체상조(P<0.05).D3조급약후24 h시가견척수경도손상.결론 초내주사우미탁미정대대서가산생항상해효응.초내주사3.00μg/kg우미탁미정항상해효응최강,단가산생단잠적척수신경독성.
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 yon Frey filaments and tail flick latency (TFL) to a thermal nociceptive stimulus were measured before (To, baseline) and at 30 or60 rin 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 c-Fos expression (by immuno-histochemistry) 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 T0 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 after 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 antinociceptive effect. High dose dexmedetomidine IT can produce transient reversible toxicity to the spinal cord.