运动训练对脊髓损伤大鼠脊髓内BDNF及mTOR表达的影响
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摘要
目的:研究运动训练对脊髓损伤(SCI)大鼠运动功能及脊髓内BDNF、mTOR表达的影响,探讨康复运动促脊髓损伤功能恢复的可能机制。方法:15只成年雌性SD大鼠随机分为假手术组、损伤对照组和运动训练组。采用通用型脊髓打击器建立大鼠T10脊髓损伤模型。损伤后7天起,对SCI大鼠进行4周运动训练,假手术组和损伤对照组不进行运动训练。损伤前及损伤后1周、2周、3周、4周、5周采用Basso Beattie Bresnahan(BBB)评分评定运动功能。运动训练结束后(即损伤后5周)取大鼠T12～L1节段脊髓,免疫组织化学检测大鼠脊髓内BDNF和mTOR表达及分布,Western blot检测大鼠脊髓内BDNF和mTOR蛋白含量。结果:BBB评分显示运动训练2～4周后SCI大鼠运动功能较假手术组、损伤对照组均有改善(P<0.05);免疫组化及Western blot结果显示运动训练组大鼠脊髓内BDNF及mTOR的表达较假手术组、损伤对照组均显著增加(P<0.05)。结论:运动训练能诱导SCI大鼠损伤脊髓内BDNF和mTOR的表达,并促进SCI大鼠运动功能的恢复。
Objective To investigate the effect of exercise on the expression of brain-derived neurotrophic factor(BDNF)and mammalian target of rapamycin(mTOR)in rats with spinal cord injury(SCI). Methods 15 adult female SD rats were divided into three groups:trial group(SCI plus exercise,n=5),control group(SCI without exercise,n=5)and sham-operation group(without SCI and exercise,n=5). SCI was produced by the universal spinal cord impact system. Exercise training began from 7th day after injury and lasted for 4 weeks. The hindlimb motor function of rats was assessed by Basso-BeattieBresnahan(BBB)scale before injury and on the 1st,2nd,3rd,4th,5th week after injury. The T12 ～ L1 spinal cords of sacrificed SCI rats were obtained after exercise on the 5th week after injury,expression of BDNF and mTOR proteins in spinal cords were detected by immunohistochemistry and Western blot.Results BBB scores from the 2nd to 4th week of exercise,and the expression of BDNF and mTOR after4 weeks of exercise in trial group were higher than in sham-operation and control groups(P < 0.05).Conclusion Exercise can effectively induce the expression of BDNF and mTOR in spinal cords and promote the recovery of hindlimb motor function of rats with SCI.
Objective To investigate the effect of exercise on the expression of brain-derived neurotrophic factor(BDNF)and mammalian target of rapamycin(mTOR)in rats with spinal cord injury(SCI). Methods 15 adult female SD rats were divided into three groups:trial group(SCI plus exercise,n=5),control group(SCI without exercise,n=5)and sham-operation group(without SCI and exercise,n=5). SCI was produced by the universal spinal cord impact system. Exercise training began from 7th day after injury and lasted for 4 weeks. The hindlimb motor function of rats was assessed by Basso-BeattieBresnahan(BBB)scale before injury and on the 1st,2nd,3rd,4th,5th week after injury. The T12 ～ L1 spinal cords of sacrificed SCI rats were obtained after exercise on the 5th week after injury,expression of BDNF and mTOR proteins in spinal cords were detected by immunohistochemistry and Western blot.Results BBB scores from the 2nd to 4th week of exercise,and the expression of BDNF and mTOR after4 weeks of exercise in trial group were higher than in sham-operation and control groups(P < 0.05).Conclusion Exercise can effectively induce the expression of BDNF and mTOR in spinal cords and promote the recovery of hindlimb motor function of rats with SCI.
引文
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[7]Ying Z,Roy RR,Edgerton VR,et al.Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.Exp Neurol,2005,193(2):411-419.
[8]Liu Y,Himes BT,Murray M,et al.Grafts of BDNF-producing fibroblasts rescue axotomizedrubrospinal neurons and prevent their atrophy.Exp Neurol,2002,178(2):150-164.
[9]Busaidy NL,Farooki A,Dowlati A,etal.Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway.J Clin Oncol,2012,30(23):2919-2928.
[10]危国军,董大明,姚猛,等.PTEN和mTOR信号转导通路在实验性脊髓损伤中的表达.现代生物医学进展,2009,9(10):1849-1851.
[11]Liu K,Lu Y,Lee JK,et al.PTEN deletion enhances the regenerative ability of adult corticospinal neurons.Nat Neurosci,2010,13(9):1075-1081.
[2]Weishaupt N,Blesch A,Fouad K.BDNF:the career of a multifaceted neurotrophin in spinal cord injury.Exp Neurol,2012,238(2):254-264.
[3]Koda M,Hashimoto M,Murakami M,et al.Adenovirus vector-mediated in vivo gene transfer of brain-derived neurotrophic factor(BDNF)promotes rubrospinal axonal regeneration and functional recovery after complete transection of the adult rat spinal cord.J Neurotrauma,2004,21(3):329-337.
[4]贺晓玉,沈慧勇,项鹏,等.人神经干细胞移植对脊髓损伤大鼠后肢运动功能恢复的影响.中国运动医学杂志,2010,29(2):208-210.
[5]黄霖,唐勇,杨睿,等.通用型脊髓打击器的研制与脊髓损伤动物模型的建立.中国脊柱脊髓杂志,2008,18(9):688-693.
[6]Bareyre FM,Kerschensteiner M,Raineteau O,et al.The injured spinal cord spontaneously forms a new intraspinal circuit in adult rats.Nat Neurosci,2004,7(3):269-277.
[7]Ying Z,Roy RR,Edgerton VR,et al.Exercise restores levels of neurotrophins and synaptic plasticity following spinal cord injury.Exp Neurol,2005,193(2):411-419.
[8]Liu Y,Himes BT,Murray M,et al.Grafts of BDNF-producing fibroblasts rescue axotomizedrubrospinal neurons and prevent their atrophy.Exp Neurol,2002,178(2):150-164.
[9]Busaidy NL,Farooki A,Dowlati A,etal.Management of metabolic effects associated with anticancer agents targeting the PI3K-Akt-mTOR pathway.J Clin Oncol,2012,30(23):2919-2928.
[10]危国军,董大明,姚猛,等.PTEN和mTOR信号转导通路在实验性脊髓损伤中的表达.现代生物医学进展,2009,9(10):1849-1851.
[11]Liu K,Lu Y,Lee JK,et al.PTEN deletion enhances the regenerative ability of adult corticospinal neurons.Nat Neurosci,2010,13(9):1075-1081.