不同浓度罗哌卡因对家兔硬膜外麻醉中脊神经的毒性作用研究
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摘要
目的探讨不同浓度罗哌卡因对家兔硬膜外麻醉中脊神经的毒性作用。方法选择无特定病原体级健康成年家兔40只,雌雄不限,L_6～L_7间隙硬膜外麻醉置管成功后,采用随机数字表法分为4组,各10只,硬膜外导管分别注射0. 2%、0.5%、1%罗哌卡因(0. 2%罗哌卡因组、0. 5%罗哌卡因组、1%罗哌卡因组)和0.9%氯化钠注射液(NS组)0.5 ml/kg,注药速度为0.05 ml/s。比较4组家兔给药前10 min,给药后10、30、60和90 min以及给药3 d后处死前的心率、收缩压、血氧饱和度以及后肢运动改良Tarlovs评分。给药3 d后对家兔进行心脏灌注处死,取脊神经制成苏木精-伊红染色冰冻切片及免疫组织化学石蜡切片,在显微镜下观察神经细胞Bcl-2的表达,通过Image-proplus计算神经细胞Bcl-2阳性细胞表达量。结果 0.5%罗哌卡因组和1%罗哌卡因组给药后30和60 min心率、收缩压、血氧饱和度均低于NS组,1%罗哌卡因组给药后30 min心率、收缩压和血氧饱和度均低于0. 5%罗哌卡因组,差异均有统计学意义(均P <0. 05)。给药后30和60 min,0.5%罗哌卡因组、1%罗哌卡因组Tarlovs评分均低于NS组(均P<0.05),0.2%罗哌卡因组与NS组比较差异均无统计学意义(均P>0. 05)。1%罗哌卡因组、0. 5%罗哌卡因组家兔脊神经Bcl-2阳性表达量高于NS组[(74. 5±2. 3)、(42. 1±4.4)比(17. 5±1. 6)],差异均有统计学意义(均P <0.01),0.2%罗哌卡因组Bcl-2阳性表达量(20.6±1.8)与NS组比较差异无统计学意义(P>0.05)。结论家兔硬膜外腔注射1%罗哌卡因后心率、血压、血氧饱和度均明显下降,后肢运动TarIovs评分明显降低,Bcl-2表达量明显升高。
Objective To analyze the toxicity of different concentrations of ropivacaine on spinal nerve in rabbits undergoing epidural anesthesia. Methods Forty specific-pathogen-free healthy adult rabbits had epidural puncture at L_6-L_7 and they were randomly divided into 4 groups( n = 10) which had epidural injection of0. 2% ropivacaine, 0. 5% ropivacaine, 1% ropivacaine and 0. 5 ml/kg 0. 9% sodium chloride solution( NS group); the drug administration rate was 0. 05 ml/s. Heart rate, systolic blood pressure, blood oxygen saturation and modified-Tarlovs score of hindlimb motor were recorded 10 min before and 10, 30, 60, 90 min, 3 d after drug administration. At 3 d after administration, the rabbits were sacrificed by heart perfusion and the spinal nerve was taken for hematoxylin-eosin frozen section and immunohistochemistry parafin section. Expression of Bcl-2 in nerve cells was observed under microscope and the Bcl-2 positive rate was calculated by Image-proplus. Results Heart rate, systolic blood pressure and blood oxygen saturation 30, 60 min after administration in the 0.5% and 1%ropivacaine groups were significantly lower than those in the NS group; heart rate, systolic blood pressure and blood oxygen saturation 30 min after administration in the 1% ropivacaine group were significantly lower than those in the 0.5% ropivacaine group( all P <0.05)) At 30 and 60 min after administration, Tarlovs score in the 0. 5%and 1% ropivacaine groups were significantly lower than that in the NS group(all P < 0. 05). Bcl-2 positive expression quantity in spinal nerve in the 1% and 0. 5% ropivacaine groups were significantly higher than that in the NS group[(74.5±2.3),(42.1±4.4) vs(17.5±1.6)](P<0. 01). Bcl-2 expression in the 0.2% ropivacaine group[(20. 6 ± 1. 8) ] was similar to that in the NS group(P >0. 05). Conclusion Epidural injection of 1%ropivacaine can significantly reduce heart rate, blood pressure, blood oxygen saturation, Tarlvos score and increase Bcl-2 expression in rabbits.
Objective To analyze the toxicity of different concentrations of ropivacaine on spinal nerve in rabbits undergoing epidural anesthesia. Methods Forty specific-pathogen-free healthy adult rabbits had epidural puncture at L_6-L_7 and they were randomly divided into 4 groups( n = 10) which had epidural injection of0. 2% ropivacaine, 0. 5% ropivacaine, 1% ropivacaine and 0. 5 ml/kg 0. 9% sodium chloride solution( NS group); the drug administration rate was 0. 05 ml/s. Heart rate, systolic blood pressure, blood oxygen saturation and modified-Tarlovs score of hindlimb motor were recorded 10 min before and 10, 30, 60, 90 min, 3 d after drug administration. At 3 d after administration, the rabbits were sacrificed by heart perfusion and the spinal nerve was taken for hematoxylin-eosin frozen section and immunohistochemistry parafin section. Expression of Bcl-2 in nerve cells was observed under microscope and the Bcl-2 positive rate was calculated by Image-proplus. Results Heart rate, systolic blood pressure and blood oxygen saturation 30, 60 min after administration in the 0.5% and 1%ropivacaine groups were significantly lower than those in the NS group; heart rate, systolic blood pressure and blood oxygen saturation 30 min after administration in the 1% ropivacaine group were significantly lower than those in the 0.5% ropivacaine group( all P <0.05)) At 30 and 60 min after administration, Tarlovs score in the 0. 5%and 1% ropivacaine groups were significantly lower than that in the NS group(all P < 0. 05). Bcl-2 positive expression quantity in spinal nerve in the 1% and 0. 5% ropivacaine groups were significantly higher than that in the NS group[(74.5±2.3),(42.1±4.4) vs(17.5±1.6)](P<0. 01). Bcl-2 expression in the 0.2% ropivacaine group[(20. 6 ± 1. 8) ] was similar to that in the NS group(P >0. 05). Conclusion Epidural injection of 1%ropivacaine can significantly reduce heart rate, blood pressure, blood oxygen saturation, Tarlvos score and increase Bcl-2 expression in rabbits.
引文
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[6] Iida H, Watanabe Y, Dohi S, et al. Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique[J]. Anesthesiology, 1997,87(1):75-81.
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[8]孙志华,郭曲练,邹望远,等.间断鞘内注射不同浓度罗哌卡因对大鼠脊髓及神经根早期超微结构的影响[J].中华麻醉学杂志,2005,25(4):283-287. DOI:10. 3760/j.issn:0254-1416.2005.04.011.Sun ZH, Guo QL, Zou WY, et al. Effect of continuous spinal anesthesia with ropivacaine on the ultrastructure of spinal cord and nerve roots in rats[J]. Chinese Journal of Anesthesiology, 2005,25(4):283-287. DOI:10.3760/j. issn:0254-1416.2005.04.011.
[9]李昊,宋春雨.丙泊酚在脑缺血再灌注中对凋亡诱导因子核转位的影响[J].实用药物与临床,2017,20(10):1107-1112.DOI:10.14053/j. cnki. ppcr.201710001.Li H, Song CY. Effects of propofol on nuclear translocation of apoptosis inducing factor during cerebral ischemia reperfusion[J].Practical Pharmacy and Clinical Remedies,2017,20(10):1107-1112. DOI:10.14053/j. cnki. ppcr.201710001.
[10]王瑛,孙志扬,张夔鸣,等.脊髓损伤后Bcl-2抗神经元凋亡的研究[J].中华急诊医学杂志,2010,19(12):1275-1280. DOI:10.3760/cma.j.issn. 1671-0282.2010.12.012.Wang Y, Sun ZY, Zhang KM, et al. Study on the role of Bcl-2 in anti-neuronal apoptosis after spinal cord injury[J]. Chinese Journal of Emergency Medicine, 2010,19(12):1275-1280. DOI:10.3760/cma. j. issn. 1671-0282.2010.12.012.
[2] Ikeya K. Neurological deficit following lumbar epidural anesthesia with ropiv acaine[J]. Masui,2007,56(8):945-948.
[3]余相地,章放香.不同老龄化程度患者硬膜外注射罗哌卡因阻滞运动神经的半数有效浓度[J].中华麻醉学杂志,2017,37(9):1121-1123. DOI:10. 3760/cma. j. issn. 0254-1416.2017.09.023.Yu XD, Zhang FX. Median effective concentration of ropivacaine blocking motor nerve in aged patients of different age stratification[J].Chinese Journal of Anesthesiology, 2017,37(9):1121-1123.DOI:10.3760/cma. j. issn. 0254-1416.2017.09.023.
[4]续飞,修培宏,高尔,等.蛛网膜下隙应用罗比卡因对家兔脊髓和脊神经根的毒性作用[J].临床麻醉学杂志,2005,21(11):776-778. DOI:10.3969/j. issn. 1004-5805.2005.11.018.Xu F, Xiu PH, Gao E, et al. The toxic effect of intrathecal ropivacaine on spinal cord and spinal nerve roots in rabbit[J]. Journal of Clinical Anesthesiology, 2005,21(11):776-778. DOI:10.3969/j. issn. 1004-5805.2005.11.018.
[5]郭艳辉,王俊科,许国忠,等.罗哌卡因用于蛛网膜下腔阻滞的实验研究[J].中华麻醉学杂志,2002,22(1):42-45.DOI:10.3760/j. issn:0254-1416.2002.01.012.Guo YH, Wang JK, Xu GZ, et al. The effect of intrathecal ropivacaine on spinal cord in dogs[J]. Chinese Journal of Anesthesiology,2002,22(1):42-45. DOI:10.3760/j.issn:0254-1416.2002.01.012.
[6] Iida H, Watanabe Y, Dohi S, et al. Direct effects of ropivacaine and bupivacaine on spinal pial vessels in canine. Assessment with closed spinal window technique[J]. Anesthesiology, 1997,87(1):75-81.
[7]张重.鞘内注射不同浓度罗哌卡因在不同时间点对大鼠脊髓神经毒性的影响及其机制的研究[D].长沙:中南大学,2009.DOI:10.7666/d.y1538389.Zhang Z. Effects of intrathecal ropivacaine of different concentrations on neurotoxicity of spinal cord in rats at different time points and its mechanism[D]. Changsha:Central South University,2009. DOI:10.7666/d.y1538389.
[8]孙志华,郭曲练,邹望远,等.间断鞘内注射不同浓度罗哌卡因对大鼠脊髓及神经根早期超微结构的影响[J].中华麻醉学杂志,2005,25(4):283-287. DOI:10. 3760/j.issn:0254-1416.2005.04.011.Sun ZH, Guo QL, Zou WY, et al. Effect of continuous spinal anesthesia with ropivacaine on the ultrastructure of spinal cord and nerve roots in rats[J]. Chinese Journal of Anesthesiology, 2005,25(4):283-287. DOI:10.3760/j. issn:0254-1416.2005.04.011.
[9]李昊,宋春雨.丙泊酚在脑缺血再灌注中对凋亡诱导因子核转位的影响[J].实用药物与临床,2017,20(10):1107-1112.DOI:10.14053/j. cnki. ppcr.201710001.Li H, Song CY. Effects of propofol on nuclear translocation of apoptosis inducing factor during cerebral ischemia reperfusion[J].Practical Pharmacy and Clinical Remedies,2017,20(10):1107-1112. DOI:10.14053/j. cnki. ppcr.201710001.
[10]王瑛,孙志扬,张夔鸣,等.脊髓损伤后Bcl-2抗神经元凋亡的研究[J].中华急诊医学杂志,2010,19(12):1275-1280. DOI:10.3760/cma.j.issn. 1671-0282.2010.12.012.Wang Y, Sun ZY, Zhang KM, et al. Study on the role of Bcl-2 in anti-neuronal apoptosis after spinal cord injury[J]. Chinese Journal of Emergency Medicine, 2010,19(12):1275-1280. DOI:10.3760/cma. j. issn. 1671-0282.2010.12.012.