利多卡因复合布比卡因或罗哌卡因鞘内注射对大鼠脊髓神经毒性的影响

摘要

Objective To observe spinal cord neurotoxicity injury induced by mixture of bupiv-acaine-lidocaine compared with mixture of ropivacaine-lidocaine.Methods Forty-eight SD rats,weig-hing 250-300 g,were randomly allocated into 6 groups (n =8):NS group (group N),1.065% bupi-vacaine group (group B),1.5% ropivacaine group (group R),5% lidocaine group (group L),mix-ture group of 5% lidocaine and 1.065% bupivacaine (group LB)or mixture group of 5% lidocaine and 1.5% ropivacaine (group LR).The rats were given intrathecal cathetering after anesthesia.Tail-flick test (TFL)and the mechanical withdrawal threshold (MWT)of rats in each group were meas-ured 1 d before operation (the baseline values)and 1 d,2 d,3 d and 4 d after intrathecal administra-tion.The movement of rat double hind legs were observed at 10 min,30 min,1 h,2 h,3 h and 4 h and 1 d,2 d,3 d and 4 d after intrathecal administration,and the changes of recovery time of lower limbs were recorded.The rats were sacrificed 4 days postoperatively followed by observation on the indexes mentioned above,and spinal cord and cauda equine were taken for staining.Then the patho-logical changes of spinal cord were observed under light and electron microscope,and caudal nerve was rated for pathological injury.Results TFLs of group LR were obviously longer than those of group N,L,B,R,LB 1-4 d after intrathecal administration (P <0.05);Compared with the group N,there was no statistical difference of TFL in the group L,B,R,LB;there was no statistically sig-nificant difference of rat MWT in comparison among the six groups at each time point.There was no statistically significant difference among six groups in recovery time of movement after intrathecal ad-ministration;and the pathological injury scores were obviously higher in group LR than that of group N,L,B,R,LB (P <0.05),respectively.Compared with the group N,there was no statistical difference of the pathological injury scores in the group L,B,R and LB,respectively.Under light microscopy observa-tion:the structure of spinal cord was normal in group N,B and R.In group L and LB,there was focal ede-ma of neurofibers.In group LR,there was edema of neurofibers or demyelination,accompanied with white mass edema in posterior horn of spinal cord.Under electron microscope,only slight edema of medullated fi-bers and unmyelinated nerve fiber was seen in group B and group R;part of the medullated fibers appeared sparse focal lamellar structure in group L and group LB;swelling and degeneration of neuraxon,separation of neuraxon from myelin sheath and disappearance of unmyelinated nerve fiber were seen in group LR. Conclusion The mixture of 5% lidocaine with 1.5% ropivacaine is more neurotoxic to spinal cord than the single administration of lidocaine or ropivacaine,moreover it is not obviously changed compared with the mixture of lidocaine with equipotent bupivacaine.%目的：探讨利多卡因复合布比卡因或罗哌卡因鞘内注射对大鼠脊髓神经毒性的影响。方法雄性 SD 大鼠48只,体重250~300 g,随机分为六组：生理盐水组(N 组)、1.065%布比卡因组(B 组)、1.5%罗哌卡因组(R 组)、5%利多卡因组(L 组)、5%利多卡因+1.065%布比卡因组(LB组)和5%利多卡因+1.5%罗哌卡因组(LR 组),每组8只。麻醉后行鞘内置管手术,于术前1 d 测定各组大鼠的甩尾潜伏期(TFL)和机械缩足阈值(MWT)作为基础值,再分别于鞘内注药后1、2、3、4 d 测试各组大鼠的 TFL 和 MWT；分别观察大鼠鞘内注药后10、30 min、1、2、3、4 h 及注药后1、2、3、4 d 各时点的双后腿运动情况,记录下肢运动恢复时间的变化。术后4 d 观察完上述指标后处死灌注,取脊髓及马尾组织染色,光镜及透射电镜下观察脊髓的病理改变,并对马尾神经进行病理损伤评分。结果鞘内注药后1~4 d LR 组 TFL 明显长于 N、L、B、R、LB 组(P <0.05)；L、B、R、LB 组与 N 组TFL 差异无统计学意义；六组大鼠各时点 MWT 差异无统计学意义。六组大鼠鞘内注射后运动恢复时间差异无统计学意义；LR 组病理损伤评分明显高于 N、L、B、R、LB 组。L、B、R、LB 组与 N 组病理损伤评分差异无统计学意义(P <0.05)。光镜观察：N、B 和 R 组脊髓结构正常。L 和 LB 组见马尾神经纤维局灶水肿。LR 组见马尾神经纤维水肿及脱髓鞘改变,伴尾段脊髓后角白质的水肿。透射电镜：B 和 R 组仅见轻微的有髓神经纤维及无髓神经纤维水肿,L 和 LB 组部分有髓神经纤维出现局灶板层结构疏松,LR 组见轴索肿胀、变型、轴索与髓鞘分离,无髓神经纤维轮廓消失。结论5%利多卡因复合1.5%罗哌卡因鞘内注射后的脊髓神经毒性较其单独注药明显增强,而复合等效浓度的布比卡因后,其脊髓神经毒性变化不明显。