中华麻醉学杂志
中華痳醉學雜誌
중화마취학잡지
CHINESE JOURNAL OF ANESTHESIOLOGY
2008年
8期
719-722
,共4页
狄美琴%连庆泉%李军%曹红
狄美琴%連慶泉%李軍%曹紅
적미금%련경천%리군%조홍
酰胺类%丁卡因%中枢神经系统%药物毒性%细胞凋亡
酰胺類%丁卡因%中樞神經繫統%藥物毒性%細胞凋亡
선알류%정잡인%중추신경계통%약물독성%세포조망
Amides%Tetracaine%Central nervous system%Drag toxicity%Apoptosis
目的 探讨不同浓度罗哌卡因对幼兔脊髓和脊神经的毒性作用.方法 日本大耳白幼兔120只,随机分为5组(n=24):0.9%生理盐水阴性对照组(S组)、2%丁卡因阳性对照组(T组)和0.25%、0.5%、0.75%罗哌卡因组(R1～3组).行L6,7穿刺后,各组于20 s内鞘内注人生理盐水、2%丁卡因或不同浓度罗哌卡因各0.2 ml.分别于鞘内给药后3、6 h、7 d时各取8只动物,行运动阻滞程度评估后处死,其中6只动物切取L5,6段脊髓,HE染色后光镜下观察脊髓病理学结果;TUNEL法检测细胞凋亡情况,计算细胞凋亡指数(AI);免疫组化法测定Bax蛋白和Bcl-2蛋白的表达水平.另2只动物切取L5,6段脊髓后角组织及神经根,透射电镜下观察脊髓和脊神经超微结构.结果 R3组可见神经胶质细胞核轻度固缩,T组脊髓出现典型凋亡细胞,其余各组脊髓和脊神经超微结构基本正常.与T组比较,R1～3>组运动阻滞显效时间延长(P<0.05);与R1组比较,R2,3组运动阻滞显效时间缩短(P<0.05). R<1～3>组与S组AI、Bax蛋白和Bcl-2蛋白表达水平差异无统计学意义(P>0.05);与T组比较,其余各组AI降低,Bax蛋白和Bcl-2蛋白表达下调(P<0.05).结论 0.25%～0.75%罗哌卡因对幼兔脊髓和脊神经无毒性作用;Bax蛋白和Bcl-2蛋白表达上调可能参与了脊髓和脊神经毒性作用的发生.
目的 探討不同濃度囉哌卡因對幼兔脊髓和脊神經的毒性作用.方法 日本大耳白幼兔120隻,隨機分為5組(n=24):0.9%生理鹽水陰性對照組(S組)、2%丁卡因暘性對照組(T組)和0.25%、0.5%、0.75%囉哌卡因組(R1～3組).行L6,7穿刺後,各組于20 s內鞘內註人生理鹽水、2%丁卡因或不同濃度囉哌卡因各0.2 ml.分彆于鞘內給藥後3、6 h、7 d時各取8隻動物,行運動阻滯程度評估後處死,其中6隻動物切取L5,6段脊髓,HE染色後光鏡下觀察脊髓病理學結果;TUNEL法檢測細胞凋亡情況,計算細胞凋亡指數(AI);免疫組化法測定Bax蛋白和Bcl-2蛋白的錶達水平.另2隻動物切取L5,6段脊髓後角組織及神經根,透射電鏡下觀察脊髓和脊神經超微結構.結果 R3組可見神經膠質細胞覈輕度固縮,T組脊髓齣現典型凋亡細胞,其餘各組脊髓和脊神經超微結構基本正常.與T組比較,R1～3>組運動阻滯顯效時間延長(P<0.05);與R1組比較,R2,3組運動阻滯顯效時間縮短(P<0.05). R<1～3>組與S組AI、Bax蛋白和Bcl-2蛋白錶達水平差異無統計學意義(P>0.05);與T組比較,其餘各組AI降低,Bax蛋白和Bcl-2蛋白錶達下調(P<0.05).結論 0.25%～0.75%囉哌卡因對幼兔脊髓和脊神經無毒性作用;Bax蛋白和Bcl-2蛋白錶達上調可能參與瞭脊髓和脊神經毒性作用的髮生.
목적 탐토불동농도라고잡인대유토척수화척신경적독성작용.방법 일본대이백유토120지,수궤분위5조(n=24):0.9%생리염수음성대조조(S조)、2%정잡인양성대조조(T조)화0.25%、0.5%、0.75%라고잡인조(R1～3조).행L6,7천자후,각조우20 s내초내주인생리염수、2%정잡인혹불동농도라고잡인각0.2 ml.분별우초내급약후3、6 h、7 d시각취8지동물,행운동조체정도평고후처사,기중6지동물절취L5,6단척수,HE염색후광경하관찰척수병이학결과;TUNEL법검측세포조망정황,계산세포조망지수(AI);면역조화법측정Bax단백화Bcl-2단백적표체수평.령2지동물절취L5,6단척수후각조직급신경근,투사전경하관찰척수화척신경초미결구.결과 R3조가견신경효질세포핵경도고축,T조척수출현전형조망세포,기여각조척수화척신경초미결구기본정상.여T조비교,R1～3>조운동조체현효시간연장(P<0.05);여R1조비교,R2,3조운동조체현효시간축단(P<0.05). R<1～3>조여S조AI、Bax단백화Bcl-2단백표체수평차이무통계학의의(P>0.05);여T조비교,기여각조AI강저,Bax단백화Bcl-2단백표체하조(P<0.05).결론 0.25%～0.75%라고잡인대유토척수화척신경무독성작용;Bax단백화Bcl-2단백표체상조가능삼여료척수화척신경독성작용적발생.
Objective To investigate the neurotoxic effects of different concentrations of ropivacaine administered intrathecally(IT) on the spinal cord and spinal nerves in young rabbits and the possible mechanism. Methods One hundred and twenty 45 day old Japanese white rabbits of either sex weighing 1.0-1.5 kg were randomly divided into 5 groups (n=24 each):group Ⅰcontrol; group Ⅱ 2% tetracaine; group Ⅲ, Ⅳ, Ⅴ 0.25%, 0.5%, 0.75% ropivacaine. The animals received 0.2 ml of normal saline (in control group), 2% tetracaine (in group Ⅱ) or 0.25 %, 0.5 %, O. 75 % ropivacaine ( in group Ⅲ, Ⅳ,Ⅴ) injected IT at L<,5-6> interspace over 20 seconds. The degree of motor block was assessed using Malinovsky scoring system (0 = normal movement, 3 = completely paralyzed) and the onset time of motor block was recorded. Eight animals each were killed at 3 h, 6 h and 7 d after IT injection. The lumbar segment (L<,5-6>) of spinal cord was immediately removed for histologic examination with electron microscope(2 animals), detection of neuronal apoptosis (by TUNEL) and determination of Bax and Bcl-2 expression (by immuno-histochemistry) (the other 6 animals). Results The animals developed different degrees of motor block in the hindlegs in the 3 repivacaine groups. The onset time became shorter with increasing concentration of ropivacaine. Electron microscopy showed that there was slight degree of nuclear shrinkage in tetracaine group. Typical apoptotic cells were also detected in the spinal cord in tetracaine group. The apoptesis index and the optical density of the cells expressing Bax or Bcl-2 were significantly lower in the control and 3 ropieaeaine groups than in tetracaine group (P < 0.05 ). Conclusions The concentration of ropivacaine 0.25 %- 0.75 % may not be injurious to the spinal cord and spinal nerves in young rabbits. The upregulation of Bax and Bcl-2 expression may be involved in the initiation and development of neurotoxicity.
