构建不同脊髓损伤节段模型大鼠下肢功能恢复的评价
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摘要
背景:研究脊髓损伤的病理生理、解剖结构等的改变,需要建立一个理想的动物模型,在选好一种损伤方式的同时选择一段安全有效的脊髓同样至关重要。目的:观察不同脊髓损伤节段对下肢功能恢复情况的影响。方法:将72只SD大鼠随机等分为6组:T_8组、T_9组、T_(10)组、T_(11)组、T_(12)组及假手术组。T_8组、T_9组、T_(10)组、T_(11)组、T_(12)组采用微型血管夹闭法分别夹闭T_8,T_9,T_(10),T_(11),T_(12)脊髓,建立脊髓损伤模型。假手术组仅切除椎板暴露硬脊膜。结果与结论:(1)T_8组、T_9组、T_(10)组、T_(11)组和T_(12)组大鼠随着造模后时间的延长,爬网格实验踏空次数减少;(2)与假手术组相比,T_8组、T_9组、T_(10)组、T_(11)组和T_(12)组大鼠的BBB评分明显降低。在损伤后第2-4周时,T_9组、T_(10)组和T_(11)组大鼠的BBB评分高于T_8组和T_(12)组,且其中T_(10)组大鼠的BBB评分高于T_9组和T_(11)组;(3)提示T_(10)是脊髓损伤后下肢功能恢复最好的节段。
BACKGROUND: An ideal animal model is essential for studies on the pathophysiologic and anatomical structures. Therefore, selecting injury method and a safe and effective segment of spinal cord is critical. OBJECTIVE: To explore the effects of different spinal cord injury segments on the recovery of lower extremity function. METHODS: Rat models of spinal cord injury at different segments were established. Seventy-two Sprague-Dawley rats were randomly divided into six groups: T_8, T_9, T_(10), T_(11), T_(12) and sham operation(laminectomy and spinal meninge exposure) groups. The rats in the T_8, T_9, T_(10), T_(11), T_(12) groups were used for establishing rat models of spinal cord injury by clipping the corresponding spinal cord segments using a microvessel clamp. RESULTS AND CONCLUSION: In the climbing grid experiment, the number of rats stepping on the air in each group decreased with time. Compared with the sham operation group, the Basso, Beattie, and Bresnahan scores in each group were significantly decreased. At 2-4 weeks after injury, the Basso, Beattie, and Bresnahan scores in the T_9, T_(10) and T_(11) groups were higher than those in the T_8 and T_(12) groups, and the scores in the T_(10) group were higher than those in the T_9 and T_(11) groups. In summary, T_(10) group showed the best recovery of lower limb function after spinal cord injury.
BACKGROUND: An ideal animal model is essential for studies on the pathophysiologic and anatomical structures. Therefore, selecting injury method and a safe and effective segment of spinal cord is critical. OBJECTIVE: To explore the effects of different spinal cord injury segments on the recovery of lower extremity function. METHODS: Rat models of spinal cord injury at different segments were established. Seventy-two Sprague-Dawley rats were randomly divided into six groups: T_8, T_9, T_(10), T_(11), T_(12) and sham operation(laminectomy and spinal meninge exposure) groups. The rats in the T_8, T_9, T_(10), T_(11), T_(12) groups were used for establishing rat models of spinal cord injury by clipping the corresponding spinal cord segments using a microvessel clamp. RESULTS AND CONCLUSION: In the climbing grid experiment, the number of rats stepping on the air in each group decreased with time. Compared with the sham operation group, the Basso, Beattie, and Bresnahan scores in each group were significantly decreased. At 2-4 weeks after injury, the Basso, Beattie, and Bresnahan scores in the T_9, T_(10) and T_(11) groups were higher than those in the T_8 and T_(12) groups, and the scores in the T_(10) group were higher than those in the T_9 and T_(11) groups. In summary, T_(10) group showed the best recovery of lower limb function after spinal cord injury.
引文
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[19]Wang Z,Mehra V,Simpson MT,et al.KLF6 and STAT3co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons.Sci Rep.2018;8(1):12565.
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[22]张富强,刘玮玮,王克平,等.行为学评价大鼠急性脊髓损伤模型脊髓节段选择的研究[J].世界科技研究与发展,2015,37(5):579-583.
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[24]肖雪飞,李娟娟,黄辉,等.天麻素对脊髓损伤模型大鼠神经功能恢复和胶质纤维酸性蛋白表达的影响[J].中国组织工程研究,2018,22(4):558-563.
[25]Tas N,Bakar B,Kasimcan MO,et al.Evaluation of protective effects of the alpha lipoic acid after spinal cord injury:an animal study.Injury.2010;41(10):1068-1074.
[26]张大威,李一帆,朱丹.急性大鼠脊髓损伤模型的建立与评估[J].中风与神经疾病杂志,2015,32(4):325-327.
[27]Kaptanoglu E,Tuncel M,Palaoglu S,et al.Comparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury.J Neurosurg.2000;93(1 Suppl):77-84.
[28]Toklu HZ,Hakan T,Celik H,et al.Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats.JSpinal Cord Med.2010;33(4):401-409.
[29]Kaymaz M,Emmez H,Bukan N,et al.Effectiveness of FK506on lipid peroxidation in the spinal cord following experimental traumatic injury.Spinal Cord.2005;43(1):22-26.
[30]Emmez H,Yildirim Z,Kale A,et al.Anti-apoptotic and neuroprotective effects ofα-lipoic acid on spinal cord ischemia-reperfusion injury in rabbits.Acta Neurochir(Wien).2010;152(9):1591-1600;discussion 1600-1601.
[31]Torres S,Salgado-Ceballos H,Torres JL,et al.Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats.Neuropathology.2010;30(1):36-43.
[2]Kumar R,Lim J,Mekary RA,et al.Traumatic Spinal Injury:Global Epidemiology and Worldwide Volume.World Neurosurg.2018;113:e345-e363.
[3]Singh A,Tetreault L,Kalsi-Ryan S,et al.Global prevalence and incidence of traumatic spinal cord injury.Clin Epidemiol.2014;6:309-331.
[4]Furlan JC,Sakakibara BM,Miller WC,et al.Global incidence and prevalence of traumatic spinal cord injury.Can J Neurol Sci.2013;40(4):456-464.
[5]Moonen G,Satkunendrarajah K,Wilcox JT,et al.A New Acute Impact-Compression Lumbar Spinal Cord Injury Model in the Rodent.J Neurotrauma.2016;33(3):278-289.
[6]张军,陈晓,张荣佳,等.脊髓损伤动物模型的研究进展[J].中华全科医学,2017,15(3):501-504.
[7]李经辉,刘禹,余化霖.脊髓损伤动物实验模型的研究进展[J].医学综述,2015,21(13):2387-2389.
[8]鲁梦倩.电针对坐骨神经损伤大鼠感觉运动传导通路中GAP-43表达影响的研究[D].北京:北京中医药大学,2013.
[9]李波霖.电针刺激对大鼠受损脊髓节段HIF-1a、VEGF表达影响的研究[D].南宁:广西中医药大学,2016.
[10]van Hedel HJ,Curt A.Fighting for each segment:estimating the clinical value of cervical and thoracic segments in SCI.JNeurotrauma.2006;23(11):1621-1631.
[11]Nguyen T,Mao Y,Sutherland T,et al.Neural progenitor cells but not astrocytes respond distally to thoracic spinal cord injury in rat models.Neural Regen Res.2017;12(11):1885-1894.
[12]Matsumoto M,Ichikawa T,Young W,et al.Glutamine synthetase protects the spinal cord against hypoxia-induced and GABA(A)receptor-activated axonal depressions.Surg Neurol.2008;70(2):122-128;discussion 128.
[13]Snyder EY,Loring JF.Beyond fraud--stem-cell research continues.N Engl J Med.2006;354(4):321-324.
[14]Jones ZB,Ren Y.Sphingolipids in spinal cord injury.Int JPhysiol Pathophysiol Pharmacol.2016;8(2):52-69.
[15]Vogelaar CF.Extrinsic and intrinsic mechanisms of axon regeneration:the need for spinal cord injury treatment strategies to address both.Neural Regen Res.2016;11(4):572-574.
[16]Yu WY,He DW.Current trends in spinal cord injury repair.Eur Rev Med Pharmacol Sci.2015;19(18):3340-3344.
[17]Tedeschi A,Bradke F.Spatial and temporal arrangement of neuronal intrinsic and extrinsic mechanisms controlling axon regeneration.Curr Opin Neurobiol.2017;42:118-127.
[18]李佳音,李星,肖志峰,等.完全性脊髓损伤再生机制的探讨[J].中国修复重建外科杂志,2018,32(6):641-649.
[19]Wang Z,Mehra V,Simpson MT,et al.KLF6 and STAT3co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons.Sci Rep.2018;8(1):12565.
[20]West H,Richardson WD,Fruttiger M.Stabilization of the retinal vascular network by reciprocal feedback between blood vessels and astrocytes.Development.2005;132(8):1855-1862.
[21]尚云龙,李一帆,宁云峰,等.大鼠脊髓损伤模型的解剖学参考定位[J].解剖学研究,2013,35(6):412-414,481.
[22]张富强,刘玮玮,王克平,等.行为学评价大鼠急性脊髓损伤模型脊髓节段选择的研究[J].世界科技研究与发展,2015,37(5):579-583.
[23]王平宇.大白鼠中枢神经系统解剖学[M].北京:人民卫生出版社,1986.
[24]肖雪飞,李娟娟,黄辉,等.天麻素对脊髓损伤模型大鼠神经功能恢复和胶质纤维酸性蛋白表达的影响[J].中国组织工程研究,2018,22(4):558-563.
[25]Tas N,Bakar B,Kasimcan MO,et al.Evaluation of protective effects of the alpha lipoic acid after spinal cord injury:an animal study.Injury.2010;41(10):1068-1074.
[26]张大威,李一帆,朱丹.急性大鼠脊髓损伤模型的建立与评估[J].中风与神经疾病杂志,2015,32(4):325-327.
[27]Kaptanoglu E,Tuncel M,Palaoglu S,et al.Comparison of the effects of melatonin and methylprednisolone in experimental spinal cord injury.J Neurosurg.2000;93(1 Suppl):77-84.
[28]Toklu HZ,Hakan T,Celik H,et al.Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats.JSpinal Cord Med.2010;33(4):401-409.
[29]Kaymaz M,Emmez H,Bukan N,et al.Effectiveness of FK506on lipid peroxidation in the spinal cord following experimental traumatic injury.Spinal Cord.2005;43(1):22-26.
[30]Emmez H,Yildirim Z,Kale A,et al.Anti-apoptotic and neuroprotective effects ofα-lipoic acid on spinal cord ischemia-reperfusion injury in rabbits.Acta Neurochir(Wien).2010;152(9):1591-1600;discussion 1600-1601.
[31]Torres S,Salgado-Ceballos H,Torres JL,et al.Early metabolic reactivation versus antioxidant therapy after a traumatic spinal cord injury in adult rats.Neuropathology.2010;30(1):36-43.