鞘内注射罗哌卡因对大鼠脊髓的神经毒性

Neurotoxic effects of intrathecal ropivacaine on spinal cord in rats

目的评价鞘内注射罗哌卡因对大鼠脊髓的神经毒性。方法取鞘内置管成功的雄性SD大鼠60只，体重180～220g，随机分为6组（n=10），分别鞘内注射0．75％布比卡因17μl（A1组）、0．75％罗哌卡因20μl（A2组）、1％罗哌卡因15μl（A3组）、0．75％布比卡因34μl（B1组）、0．75％罗哌卡因40μl（B2组）和1％罗哌卡因30μl（B3组）。注药后记录出现双后肢瘫痪时间和运动功能恢复情况。注药后6h取腰膨大处脊髓，采用免疫组织化学法计数fos蛋白阳性细胞，测定fos蛋白表达；采用RT—PER技术测定c—los mRNA表达；透射电镜观察脊髓超微结构。结果与A1组比较，气组和B3组出现双后肢瘫痪时间缩短，B1组fos蛋白阳性细胞计数和fos蛋白表达升高（P〈0．01）；与A2组比较，A3组和B2组出现双后肢瘫痪时间缩短，助组fos蛋白阳性细胞计数和fos蛋白表达升高（P〈0．01）；与气组、B1组和B2组比较，B3组出现双后肢瘫痪时间缩短，双后肢运动功能恢复率降低，fbs蛋白阳性细胞计数、fos蛋白表达和c—fos mRNA表达均升高（P〈0．01），脊髓损伤加重。结论鞘内注射0．75％罗哌卡因和小剂量1％罗哌卡因对大鼠无脊髓神经毒性；鞘内注射大剂量1％罗哌卡因对大鼠可产生脊髓神经毒性，但比大剂量0．75％布比卡因脊髓神经毒性小。

Objective To evaluate the neurotoxic effects of intrathecal （IT） ropivacaine on the spinal cord in rats. Methods Sixty healthy male SD rats weighing 180-220 g in which IT catheters were successfully placed according to Yaksh TL were randomly divided into 6 groups （n = 10 each）. The animals received 0.75% bupivacaine 17 μl （group A1 ）; 0.75% ropivacaine 20μl （group A2 ） and 1% ropivacaine 15μl （group A3 ） IT respectively. The volumes of IT bupivacaine/ropivacaine were doubled in group B： 075 % bupivacaine 34 μl （group BI ） ; 0.75% ropivacaine 40 μl （group B2 ） and 1% ropivacaine 30μl （group B3 ） . The onset time of bilateral hindlimb paralysis and recovery time were recorded. The animals were killed at 6 h after IT bupivacaine/ ropivacaine injection. The lumbar segment of the spinal cord was removed for microscopic examination with electron microscope and determination of expression of c-los mRNA （by RT-PCR） and protein （by immuno- histochemistry）. Results The onset time of hindlimb paralysis was shorter in group A3 and B1 and the number of fos-protein positive cells and the expression of los-protein were significantly higher in group B1 than in group A1 The onset time of hindlimb paralysis was shorter in group A3 and B2 and the number of fos-protein positive cells and the expression of fos-protein were significantly higher in group B2 than in group A2 . The onset time of paralysis was shorter, the rate of recovery of motor function of bilateral hindlimbs was lower, the number of los-protein positive cells and expression of fos-protein and mRNA were significantly higher and spinal cord injury was severer in group B3 than in group A3 , B1 and B2 .Conclusion 0.75% and small dose of 1% ropivacaine administered IT do not produce neurotoxicity to the spinal cord while large dose of 1% ropivacaine can produce neurotoxicity which is less severe than that produced by large dose of 0.75 % bupivacaine.