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中华神经创伤外科电子杂志 ›› 2015, Vol. 01 ›› Issue (03) : 158 -163. doi: 10.3877/cma.j.issn.2095-9141.2015.03.009

基础研究

拉莫三嗪对小鼠脊髓背侧半横断损伤的保护作用
付强1, 王兆涛2, 张茂营2, 徐如祥2,()   
  1. 1.100853 北京,解放军医学院
    2.100700,北京军区总医院附属八一脑科医院
  • 收稿日期:2015-04-23 出版日期:2015-06-15
  • 通信作者: 徐如祥
  • 基金资助:
    军队十二五重大科技项目(BWS12J010)

Protective effect of lamotrigine on mouse dorsal spinal cord injury

Qiang Fu1, Zhaotao Wang, Maoying Zhang, Ruxiang Xu()   

  1. 1.Medical School of Chinese PLA,Beijing 100853, China
  • Received:2015-04-23 Published:2015-06-15
  • Corresponding author: Ruxiang Xu
引用本文:

付强, 王兆涛, 张茂营, 徐如祥. 拉莫三嗪对小鼠脊髓背侧半横断损伤的保护作用[J]. 中华神经创伤外科电子杂志, 2015, 01(03): 158-163.

Qiang Fu, Zhaotao Wang, Maoying Zhang, Ruxiang Xu. Protective effect of lamotrigine on mouse dorsal spinal cord injury[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(03): 158-163.

目的

探讨拉莫三嗪在小鼠脊髓损伤修复中的作用。

方法

雌性C57BL/6 小鼠80只采用脊髓背侧半横断损伤模型,随机分为模型组:单纯脊髓损伤;治疗组:脊髓损伤后每天给予腹腔注射拉莫三嗪,按照25 mg/kg的计量,连续7 d;对照组:脊髓损伤后每天给予腹腔注射0.9%生理盐水,按照25 mg/kg的计量,连续7 d。术后分别在1 d、7 d、14 d对各组小鼠行BBB评分,并分别在1 d、7 d、14 d在各组随机抽取6只小鼠,进行免疫荧光染色观察胶质细胞变化,并在术后第7天各组取6只小鼠组织行ELISA检测,观察炎症因子表达情况。

结果

损伤后7、14 d治疗组小鼠BBB评分明显高于模型组和对照组,差异有统计学意义(P<0.05);脊髓损伤后矢状切面损伤灶下游的GFAP+(星形胶质细胞的标记)细胞的免疫荧光面积百分比,发现术后7 d和14 d治疗组(9.87±0.96,4.79±1.02)的明显低于模型组(12.34±1.72,7.46±1.28)和对照组(11.89±1.70,7.53±1.70),差异均有统计学意义(P<0.05)。ELISA 检测术后7 d 小鼠T9~T11 的IL-1、IL-10、TNF-α表达情况,IL-1、IL-10的表达治疗组明显低于模型组和对照组,差异有统计学意义(P<0.05)。

结论

拉莫三嗪可以改善脊髓损伤小鼠的运动功能,通过前期减少炎症因子的分泌降低胶质细胞的活化来实现的。

Objective

To investigate the effect of lamotrigine (LTG) on recovery after spinal cord injury(SCI).

Methods

A total of 80 female C57BL/6 mouses were made the model of spinal cord hemisection, and all of these were randomly divided into 3 group:SCIgroup,SCI+LTG group and SCI+0.9%saline group;mouses in SCI+LTG grouop were given interperitoneal injection of lamotrigine(25 mg/kg)for 7days,and mouses in SCI+0.9%saline group were given the same volume of 0.9%saline.Basso,Beatti,Bresnahan(BBB)scale was perfomed 1,7,14days after SCI;the number of glial cell were observed by immunofluorescence and the express of inflammatory factors were obseverd by ELISA(enzyme linked immunosorbent assay).

Results

On the 7th, 14th days after injury, the BBB scale scores in the SCI+LTG group were significantly higher than those in the SCI group and in the SCI+0.9%saline group (P<0.05). On the 7th, 14th days after injury, less percentage of GFAP+ fluorenscent area and less number of Iba1+cells in the SCI+LTG group were distributed in the lesion area than those in the SCI group and in the SCI+0.9%saline group(P<0.05).On the 7th day after spinal cord injury,the IL-1 and IL-10 expression in SCI+LTG group were obviously lower than those in the SCI group and in the SCI+0.9% saline group(P<0.05).

Conclusion

Lamotrigine improve the motor function after spinal cord injury by decrease the activation of the glial cells.

表1 各组小鼠不同时间点BBB评分(±s)
表2 各组小鼠不同时间点GFAP+荧光面积百分比(%)(±s)
表3 各组小鼠不同时间点Iba1+相对面积下数目(cells/mm2)(±s)
图1 免疫荧光染色三组小鼠GFAP+(星形胶质细胞)数量变化 A:SCI 组Day1;B:SCI 组Day7;C:SCI 组Day14;D:SCI+LTG 组Day1;E:SCI+LTG 组Day7;F:SCI+LTG 组Day14;G:SCI+0.9%saline 组Day1;H:SCI+0.9%saline组Day7;I:SCI+0.9%saline组Day14
图2 免疫荧光染色三组小鼠Iba1+(小胶质细胞)数量变化 A:SCI 组Day1;B:SCI 组Day7;C:SCI 组Day14;D:SCI+LTG 组Day1;E:SCI+LTG 组Day7;F:SCI+LTG 组Day14;G:SCI+0.9%saline 组Day1;H:SCI+0.9%saline组Day7;I:SCI+0.9%saline组Day14
表4 第7天炎症因子在各组小鼠表达情况(±s)
[1]
邹明明,薛兴森,朱海涛,等.姜黄素促进大鼠脊髓损伤恢复的病理及行为学研究[J]. 第三军医大学学报, 2011, 33(8):765-770.
[2]
Popiolek- Barczyk K, Kolosowska N, Piotrowska A, et al.Parthenolide Relieves Pain and PromotesM2 Microglia/Macrophage Polarization in Rat Model of Neuropathy[J].Neural Plasticity,2015,2015.
[3]
Tsuda M. [Mechanisms underlying the pathogenesis of neuropathic pain revealing by the role of glial cells] [J]. Nihon shinkei seishin yakurigaku zasshi= Japanese journal of psychopharmacology,2015,35(1):1-4.
[4]
Clark AK, Gruber-Schoffnegger D, Drdla-Schutting R, et al.Selective Activation of Microglia Facilitates Synaptic Strength[J].The Journal of Neuroscience,2015,35(11):4552-4570.
[5]
Berliocchi L, Maiarù M, Varano GP, et al. Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain[J].Molecular pain,2015,11(1):3.
[6]
Yin Q, Fan Q, Zhao Y, et al. Spinal NF-κB and Chemokine Ligand 5 Expression during Spinal Glial Cell Activation in a Neuropathic Pain Model[J].PloS one,2015,10(1):e0115120.
[7]
Choi YS, Jun IG, Kim SH, et al. Intrathecal Lamotrigine Attenuates Mechanical Allodynia and Suppresses Microglial and Astrocytic Activation in a Rat Model of Spinal Nerve Ligation[J].Yonsei medical journal,2013,54(2):321-329.
[8]
Dag E, Dag ZO, Baydas G, et al. Effects of lamotrigine and topiramate on brain maturation and cognitive functions in offspring of pregnant rats-preliminary study[J]. Advances in clinical and experimental medicine: official organ Wroclaw Medical University,2014,23(5):691.
[9]
Floriddia EM, Rathore KI,Tedeschi A, et al. p53 Regulates the neuronal intrinsic and extrinsic responses affecting the recovery of motor function following spinal cord injury[J]. The Journal of Neuroscience,2012,32(40):13956-13970.
[10]
Zhang MY, Zheng CY, Zou MM, et al. Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice[J]. Neurobiology of aging,2014,35(12):2713-2725.
[11]
张鸿日,彭静华,张茂营,等.2ME2 对脊髓损伤大鼠运动功能及Tau 蛋白磷酸化的影响[J].中华神经医学杂志,2014,13(011):1127-1130.
[12]
Nunes AF, Amaral JD, Lo AC, et al. TUDCA, a bile acid,attenuates amyloid precursor protein processing and amyloid-β deposition in APP/PS1 mice[J]. Molecular neurobiology, 2012,45(3):440-454.
[13]
Wiffen PJ, Derry S, Moore RA. Lamotrigine for acute and chronic pain[J].The Cochrane Library,2011.
[14]
Marchand F, Perretti M, McMahon SB. Role of the immune system in chronic pain[J]. Nature Reviews Neuroscience, 2005,6(7):521-532.
[15]
Poonuru RR, Gonugunta CSR. Bimodal gastroretentive drug delivery systems of lamotrigine: Formulation and evaluation[J].Indian journal of pharmaceutical sciences,2014,76(6):476.
[16]
Kishimoto A, Goto Y, Hashimoto K. Post- traumatic Stress Disorder Symptoms in a Female Patient Following Repeated Teasing: Treatment with Gabapentin and Lamotrigine and the Possible Role of Sensitization[J]. Clinical Psychopharmacology and Neuroscience,2014,12(3):240-242.
[17]
Jun IG, Kim SH, Yoon YI, et al. Intrathecal lamotrigine attenuates antinociceptive morphine tolerance and suppresses spinal glial cell activation in morphine-tolerant rats[J]. Journal of Korean medical science,2013,28(2):300-307.
[18]
Perisic T, Zimmermann N, Kirmeier T, et al. Valproate and amitriptyline exert common and divergent influences on global and gene promoter- specific chromatin modifications in rat primary astrocytes[J]. Neuropsychopharmacology, 2010, 35(3):792-805.
[19]
Guizzo R, Paques MW, Anhezini L, et al. Neuroprotective effects of oral lamotrigine administration on rabbit retinas after pars plana vitrectomy and silicone oil injection[J]. Retina,2008,28(4):638-644.
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