盐酸氨溴索联合大剂量甲基强的松龙冲击治疗促进胸腰椎骨折合并脊髓损伤术后神经功能恢复作用的初步探讨

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (8): 937-942.

盐酸氨溴索联合大剂量甲基强的松龙冲击治疗促进胸腰椎骨折合并脊髓损伤术后神经功能恢复作用的初步探讨

张朋¹，陈勇忠²，王金星¹，张金锋¹，翁超群¹，叶忠兴¹

¹福建三博福能脑科医院神经外科，福州 350001，福建； ²南京军区福州总院四七六医院骨科，福州 350002，福建

收稿日期:2017-03-31 修回日期:2017-05-10 出版日期:2017-08-26 发布日期:2017-08-18
通讯作者: 王金星，男，硕士研究生，副主任医师，研究方向：脊柱脊髓相关疾病及小儿脑瘫的诊治。 Tel：13705979508 E-mail：wjxing1005@126.com
作者简介:张朋，男，硕士研究生，主治医师，研究方向：脊柱脊髓及疼痛相关疾病的诊断和治疗。 Tel：15980151980E-mail：dr.zpeng@hotmail.com
基金资助:
福建省自然科学基金（2015J01494）

Effect of ambroxol hydrochloride combined with high-dose methylprednisolone therapy on the recovery of neurological function after spinal cord injury in patients with thoracolumbar fractures

ZHANG Peng¹, CHEN Yongzhong ², WANG Jinxing¹ , ZHANG Jinfeng ¹, WENG Chaoqun ¹, YE Zhongxing¹

¹ Department of Neurosurgery, Fujian Sanbo Funeng Brain Hospital, Fuzhou 350001, Fujian, China; ²Department of Orthopedics, the 476th Hospital of Fuzhou General Hospital of Nanjing Military Region, Fuzhou 350002, Fujian, China

Received:2017-03-31 Revised:2017-05-10 Online:2017-08-26 Published:2017-08-18

摘要/Abstract

摘要：

目的: 初步探讨盐酸氨溴索联合大剂量甲基强的松龙（methylprednisolone，MP）冲击治疗对胸腰椎骨折合并急性脊髓损伤术后神经功能恢复的作用。方法: 选取2015年2月至2016年8月在南京军区福州总院四七六医院骨科就诊并急诊手术治疗的胸腰椎骨折患者合并脊髓损伤患者48例作为研究对象。按随机数字表法分为联合治疗组和对照组，每组24例。2组均根据脊髓受压程度急诊实施椎管减压及植骨融合内固定手术，在15 min内经静脉快速滴注总量为30 mg/kg的MP（冲击治疗），45 min后继续给予5.4 mg·kg-1·h-1的MP，持续时间为23 h。联合治疗组：在对照组基础上，给予静脉滴注盐酸氨溴索（60 mg/次，q12h），持续治疗30 d。2组患者均给予抗感染、止血、脱水及对症治疗，并静脉滴注奥美拉唑（30 mg/次,q12h，持续3 d）预防消化道应激性溃疡发生。随访6个月，依据Frankel分级法判定2组治疗后临床疗效，评估比较2组患者治疗前、治疗后1个月、6个月各时间点的ASIA感觉、运动评分；并记录2组的药物不良反应发生情况。结果: 2组患者基线资料如年龄、性别比、体质量指数等比较，差异无统计学意义（P>0.05）；经治疗后第6个月联合治疗组总有效率显著高于对照组（87.5% vs. 62.5%，P<0.05）；2组患者在治疗第1个月、6个月ASIA感觉、运动评分均较治疗前明显升高（P<0.05），与对照组相比，联合治疗组感觉、运动评分在治疗后第1个月、6个月显著升高（P<0.05）；在不良反应发生情况方面，联合治疗组和对照组比较差异无统计学意义（29.2% vs. 33.3%，P>0.05）。结论: 盐酸氨溴索联合大剂量MP冲击治疗可显著改善胸腰椎骨折合并急性脊髓损伤患者的神经损伤程度，促进神经功能恢复，较单一MP冲击治疗效果更佳，但仍需更多临床和实验室研究进一步证实。

关键词: 盐酸氨溴索, 甲基强的松龙, 胸腰椎骨折合并脊髓损伤, 神经功能

Abstract:

AIM: To discuss the therapeutic effect of ambroxol hydrochloride combined with high-dose methylprednisolone (MP) on the recovery of neurological function after spinal cord injury in patients with thoracolumbar fractures. METHODS: Forty eight patients with thoracolumbar fractures plus spinal cord injury admitted to our hospital from Feburary 2016 to August 2016 were randomly divided into the combination group and the control group according to random number table (n=24). All the patients were performed decompression and internal fixation operation, and MP was given 30 mg/kg intravenously for 15 min, another 5.4 mg·kg-1·h-1 MP was given intravenously for 23 h 45 minutes later. Based on the treatment of the control group, the combination group received extra ambroxol hydrochloride intravenously (60 mg/time, 1 time/12 h), continued for 30 days. Patients in both groups were given anti-infection, hemostatic, dehydration, and symptomatic treatment, and intravenous drip of omeprazole (30 mg/time, 1 time/12 h, 3 d) was administered to prevent gastrointestinal stress ulcer. All patients were followed up for 6 months; the clinical curative effect in two groups were determined according to Frankel classification method; ASIA sensory and motor score were evaluated and compared between two groups before and 1 month and 6 month after treatment; adverse drug reactions were recorded. RESULTS:No statistically significant difference were observed with the baseline data such as age,sex,heart rate,breathing and body mass index between the two groups(P>0.05).After 6 months' treatment,the total effective rate in the combination group was significantly higher than that of the control group (87.5% vs. 62.5%, P<0.05); ASIA sensory and motor score were significantly elevated compared with before treatment in both groups 1 month and 6 month after treatment (P<0.05), and between the two groups, the combination group presented more significant improvement (P<0.05); No statistically significant difference was observed with adverse reaction occurrence between the two groups (29.2% vs. 33.3%, P>0.05).CONCLUSION:Compared with simple MP shock treatment, ambroxol hydrochloride combined with high-dose MP can significantly alleviate the injured neurological function and improve neural functional recovery in patients with thoracolumbar fractures combined with spinal cord injury, whereas more clinical and laboratory research are needed to confirm the effect.

Key words: ambroxol hydrochloride, methylprednisolone, thoracolumbar fractures combined with spinal cord injury, neurological function

中图分类号:

R683.2

张朋，陈勇忠，王金星，张金锋，翁超群，叶忠兴. 盐酸氨溴索联合大剂量甲基强的松龙冲击治疗促进胸腰椎骨折合并脊髓损伤术后神经功能恢复作用的初步探讨[J]. 中国临床药理学与治疗学, 2017, 22(8): 937-942.

ZHANG Peng, CHEN Yongzhong, WANG Jinxing, ZHANG Jinfeng, WENG Chaoqun, YE Zhongxing. Effect of ambroxol hydrochloride combined with high-dose methylprednisolone therapy on the recovery of neurological function after spinal cord injury in patients with thoracolumbar fractures[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(8): 937-942.

参考文献

［1］桂彤, 杨超, 何炳书, 等. 急性脊髓损伤早期应用大剂量甲基泼尼松龙辅助治疗效果观察［J］. 山东医药, 2016, 56(42): 65-66.
［2］曹鹏, 石长贵, 袁文, 等. 甲基强的松龙在急性脊髓损伤中的应用进展［J］. 中国脊柱脊髓杂志, 2015, 25(2): 174-178.
［3］朱庄臣, 焦伟, 蔡国栋, 等. 大剂量甲强龙治疗急性脊髓损伤后早期并发症的研究［J］. 中国矫形外科杂志, 2014, 22(16): 1454-1457.
［4］Brooks NP, Potts E, O`Toole J. Letter: The impact of guidelines on clinical practice: survey of the use of methylprednisolone for acute spinal cord injury［J］. Neurosurg, 2016, 79(3): E516-E520.
［5］Weiser T. Ambroxol: a CNS drug［J］? CNS Neurosci Ther, 2008, 14(1): 17-24.
［6］Gaida W, Klinder K, Arndt K, et al. Ambroxol, a Nav1.8-preferring Na(+) channel blocker, effectively suppresses pain symptoms in animal models of chronic, neuropathic and inflammatory pain［J］. Neuropharmacol, 2005, 49(8): 1220-1227.
［7］Chandran V, Coppola G, Nawabi H, et al. A systems-level analysis of the peripheral nerve intrinsic axonal growth program［J］. Neuron, 2016, 89(5): 956-970.
［8］Mbori NJ, Chuan XY, Feng QX. Evaluation of the combination of methylprednisolone and tranilast after spinal cord injury in rat models［J］. J Korean Neurosurg Soc, 2016, 59(4): 334-340.
［9］王一吉, 周红俊, 李建军, 等. 脊髓损伤神经学分类国际标准检查表最新修订及解读［J］.中国康复理论与实践, 2015, 21(8): 879-882.
［10］关骅, 陈学明. 脊髓损伤ASIA神经功能分类标准(2000年修订)［J］. 中国脊柱脊髓杂志, 2001, 11(3): 164.
［11］李小群, 杨利学, 吕正, 等. 椎弓根固定系统治疗胸腰椎骨折合并脊髓损伤57例分析［J］. 长春中医药大学学报, 2009, 25(5): 702-704.
［12］陈勇, 夏刚. Rho激酶抑制剂联合高压氧对胸腰椎骨折合并脊髓损伤术后神经功能恢复的效果观察［J］. 中国生化药物杂志, 2015, 35(10): 85-87.
［13］Lu GB, Niu FW, Zhang YC, et al. Methylprednisolone promotes recovery of neurological function after spinal cord injury: association with Wnt/β-catenin signaling pathway activation［J］. 2016, 11(11): 1816-1823.
［14］曹奇, 唐晓军, 李贵涛, 等. 围手术期应用甲基强的松龙与地塞米松对脊髓型颈椎病髓内高信号转归及临床意义的比较［J］. 中国矫形外科杂志, 2013, 21(3): 217-222.
［15］Celik H, Karatay M, Erdem Y, et al. The biochemical, histopathological and clinical comparison of the neuroprotective effects of subcutaneous adalimumab and intravenous methylprednisolone in an experimental compressive spinal cord trauma model ［J］. Turk Neurosurg, 2016, 26(4): 622-631.
［16］ Evaniew N, Noonan VK, Fallah N, et al. Methylprednisolone for the treatment of patients with acute spinal cord injuries: response［J］. J Neurotrauma, 2016, 33(10): 975-976.
［17］Afshari FT, Kappagantula S, Fawcett JW. Extrinsic and intrinsic factors controlling axonal regeneration after spinal cord injury［J］. Expert Rev Mol Med, 2009, 11: e37.
［18］Hollis ERⅡ. Axon guidance molecules and neural circuit remodeling after spinal cord injury［J］. Neurotherapeutics, 2016, 13(2): 360-369.

[1]	吴志勇, 刘兵荣, 李彬, 汤睿. 红细胞分布宽度对急性缺血性卒中静脉溶栓早期神经功能改善不良的预测作用[J]. 中国临床药理学与治疗学, 2023, 28(3): 307-314.
[2]	蒋豪明，陈翔，李珍，顾承萍. 单唾液酸四己糖神经节苷脂联合鼠神经生长因子对新生儿缺氧缺血性脑病的临床研究[J]. 中国临床药理学与治疗学, 2019, 24(3): 301-306.
[3]	马远东，黄祖伟，安培，谢晓菲，刘小彩，毛凌哲. 盐酸氨溴索治疗大鼠肺纤维化的作用研究及其对TGF-β/Smad/ERK信号转导通路和Th17/Treg细胞失衡的影响[J]. 中国临床药理学与治疗学, 2018, 23(11): 1201-1208.
[4]	谢跃武，张芳，郭岩. 小鼠大脑中动脉栓塞模型脑血流量与梗死体积相关性分析[J]. 中国临床药理学与治疗学, 2017, 22(5): 501-506.
[5]	罗玲玲，滕承志，李晓笑，潘丹峰. 阿奇霉素联合盐酸氨溴索治疗小儿支原体肺炎合并急性支气管炎的临床研究[J]. 中国临床药理学与治疗学, 2017, 22(11): 1278-1282.
[6]	方声，王丽珍. 脑苷肌肽对缺氧缺血性脑病血清胰岛素样生长因子1及治疗预后的影响[J]. 中国临床药理学与治疗学, 2017, 22(1): 72-76.
[7]	李春林，唐世雄，张立涛，陆徐，王耀文，孔德秋，程鹏，包卫亮. 三种不同甲基强的松龙给药方法治疗突发性耳聋的临床分析[J]. 中国临床药理学与治疗学, 2016, 21(11): 1302-1305.
[8]	罗胜勇, 叶寿山, 李睿, 贾德云, 李心伟, 马征, 陈志武, 李小羿, 张国辉, 戴向荣. 抗血小板溶栓素对局灶性脑缺血/再灌注大鼠脑损伤的作用观察[J]. 中国临床药理学与治疗学, 2015, 20(3): 274-278.
[9]	何庆璋. 葛根素与复方丹参注射液联用对急性高血压脑出血患者神经功能的改善作用[J]. 中国临床药理学与治疗学, 2012, 17(9): 1057-1061.
[10]	刘珺, 王均炉, 胡祥鹏, 厉彩霞, 彭玲莉. 人组织激肽释放酶对周围神经系统损伤后的修复效应[J]. 中国临床药理学与治疗学, 2009, 14(12): 1351-1355.
[11]	罗慧英, 程体娟. 甘西鼠尾草注射液与丹参注射液对大鼠缺血再灌注损伤保护作用的比较[J]. 中国临床药理学与治疗学, 2008, 13(9): 972-975.
[12]	李榕, 罗春霞, 迟路湘. 重组人生长激素对局灶性脑缺血大鼠神经功能恢复的影响[J]. 中国临床药理学与治疗学, 2007, 12(11): 1288-1291.
[13]	蒋亚斌. 氟西汀治疗脑卒中后抑郁对照研究的 Meta 分析[J]. 中国临床药理学与治疗学, 2006, 11(1): 74-77.
[14]	王睿, 周筱青, 陈马昆, 周践, 魏荣, 董军, 曹秀堂, 周亚春, 王瑾, 郭代红, 王洁松, 朱秀美, 梁蓓蓓, 徐艳萍, 周先志. SARS 患者应用甲基强的松龙注射剂治疗情况与不良反应分析[J]. 中国临床药理学与治疗学, 2004, 9(9): 992-996.
[15]	李超, 卢娜, 李东亮, 张剑凯. 黄体酮防治大鼠缺血再灌注脑损伤中神经功能缺失及细胞凋亡[J]. 中国临床药理学与治疗学, 2004, 9(9): 1045-1049.