BDNF在大鼠脊髓压迫性损伤脱髓鞘病变中的作用
The role of BDNF on demyelination after compressed spinal cord injury in rat
目的 观察脊髓压迫性损伤后脑源性神经生长因子（Brain-derived neurotrophic factor，BDNF）的表达变化与有髓神经纤维脱髓鞘病变之间的关系，以阐明BDNF对神经纤维脱髓鞘病变的作用。 方法 SD雄性大鼠60只，将其均分成3 组：模型组、假手术组和正常组，用自行设计的压迫器制作大鼠脊髓压迫模型。模型组作脊髓压迫24 h, 假手术组仅作脊髓显露,不作压迫。锇酸和LFB(luxol fast blue) 染色观察有髓神经纤维变化情况； Western blot检测髓鞘碱性蛋白( myelin basic protein，MBP)和BDNF的表达。 结果 24 h后，与假手术组比较，模型组压迫前段(T11)有髓神经纤维无明显肿胀和数量变化，MBP表达未见变化（P>0.05），但BDNF的表达量升高(P<0.05)；而压迫段（T12）和压迫后段（L1）有髓神经纤维肿胀并伴有数量降低(P<0.05), BDNF和MBP的表达量也随之下降(P<0.05)，且压迫段（T12）脱髓鞘病变更为严重，BDNF降低也更为明显(P<0.01)。 结论 大鼠脊髓压迫性损伤BDNF表达减少可导致脊髓脱髓鞘病变的发生，而BDNF表达量升高可能对脊髓脱髓鞘病变具有保护作用。
Objective The objective of this study was to observe the relationship between the expression of brain-derived neurotrophic factor (BDNF) and the demyelinating of the myelinated nerve fibers after compressed spinal cord injury (CSCI) and to clarify the role of BDNF in demyelination. Methods 60 male SD rats were divided into 3 groups evenly and randomly：a model group，a sham group and a normal group. The CSCI rat model was established by a self-designed compression device. For the model group, 24h spinal cord compression was given; spinal cord exposition was made to the sham group, with no compression; and nothing was done to the normal group. Osmic acid and luxol fast blue (LFB) staining were used for observing the changes of myelinated nerve fibers. Expression of BNDF and MBP(myelin basic protein) were identified by Western-blot analysis. Results 24h after CSCI，the myelinated nerve fibers had no obvious swelling or change in number in the compressed anterior (T11); but there were excessive swelling and decrease in number in the compressed part (T12) and inferior to the compressed part (L1) (P<0.05). In the compressed anterior (T11), MBP expression was unchanged (P>0.05) 24h after CSCI and the expression of BDNF increased (P<0.05). On the contrary, both MBP and BDNF expression decreased in the compressed part(T12) and the compressed posterior(L1) (P<0.05). And the demyelination was more serious in the compressed part with significant reduction in BDNF (P<0.01). Conclusion Decreased expression of BNDF can lead to demyelination after CSCI , while increased expression of BNDF may have protective effect on demyelination.
脊髓压迫性损伤 / 脱髓鞘 / 脑源性神经生长因子 / 髓鞘碱性蛋白 / 大鼠
Compressed spinal cord injury / Demyelination / Brain-derived neurotrophic factor / Myelin basic protein / Rats
[1] All AH,Bazley FA,Gupta S,et al.Human embryonic stem cell-derived oligodendrocyte progenitors aid in functional recovery of sensory pathways following contusive spinal cord injury[J]. PLoS One, 2012, 7(10): 1-11.
[2] Huang SQ，Tang CL，Sun SQ，et al.Demyelination initiated by oligodendrocyte apoptosis through enhancing endoplasmic reticulum-mitochondria interactions and Id2 expression after compressed spinal cord injury in rats[J]. CNS Neurosci Ther，2014,20(1): 20-31.
[3] Kuboyama K，Fujikawa A，Masumura M，et al．Protein tyrosine phosphatase receptor type z negatively regulates oligodendrocyte differentiation and myelination［J］.PLoS One，2012，7(11):e48797．
[4] Sharma HS. Neurotrophic factors attenuate microvascular permeability disturbances and axonal injury following trauma to the rat spinal cord[J]. Acta Neurochir Suppl, 2003,8(6): 383-388.
[5] Nakajima H,Uchida K, Kobayashi S,et al.Rescue of rat anterior horn neurons after spinal cord injury by retrograde transfection of adenovirus vector carrying brain-derived neurotrophic factor gene[J].Nerotrauma, 2007,24(4): 703-712．
[6] 梁益建，孙善全，汪克建，等．大鼠脊髓慢性压迫性损伤实验模型的建立[J]．中国临床解剖学杂志，2006，24(3): 318-324．
[7] Barde YA,Edgar D,Thoenen H.Purification of a new neurotrophic factor from mammalian brain[J]. EurMolecBiologJ, 1982,25(1):549-53.
[8] Balkowiec A,Katz DM.Activity-dependent release of endogenous brain-derived neurotrophic factor from primary sensory neurons detected by ELISA in situ[J]. J Neurosci, 2000,20(3): 7417-7423.
[9] Brock JH, Rosenzweig ES, Blesch A,et al. Local and remote growth factor effects after primate spinal cord injury[J]. J Neurosci, 2010, 30(29): 9728-9737.
[10] Singh KK，Park KJ，Hong EJ．Developmental axon pruning mediated by BDNF-p75NTR-dependent axon degeneration［J］．Nat Neurosci，2008，11(6): 649-658．
[11] IkedaO,MurakamiM,InoH,et al.Acute up-regulation of brain-derived neurotrophic factor expression resulting from experimentally induced injury in the rat spinal cord[J]. Acta Neuropathol, 2001,102(3): 239-245.
[12] Wang H,Wu LL,Song XY, et al.Axonaltransport of BDNF precureor in primary sensory neurons[J]. Eur J Neurosci，2006, 24(9): 2444-2452.
国家青年科学基金（81403466）
京ICP备08002354号-3/
| 〈 |
|
〉 |
