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李向哲,王红星,谢财忠,吴勤峰,宋新建,曹雅娜,方 露,丁 洁,王 彤.阻断脑源性神经营养因子-酪氨酸激酶受体B通路后运动训练对脊髓损伤大鼠功能恢复的影响研究[J].中国康复医学杂志,2017,(12):1331~1337
阻断脑源性神经营养因子-酪氨酸激酶受体B通路后运动训练对脊髓损伤大鼠功能恢复的影响研究    点此下载全文
李向哲  王红星  谢财忠  吴勤峰  宋新建  曹雅娜  方 露  丁 洁  王 彤
南京医科大学第一临床医学院,南京,210029
基金项目:国家自然科学基金面上项目(81171851)
DOI:
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摘要:
      摘要 目的:探讨阻断脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)-酪氨酸激酶受体B(tropomyosin-related kinase B,TrkB)信号通路后运动训练对脊髓损伤(spinal cord injury,SCI)大鼠运动功能恢复和突触可塑性的影响。 方法:32只雌性SD大鼠被随机分为4组:损伤+PBS组(Sed-PBS组)、运动+PBS组(TT-PBS组)、损伤+TrkB/Fc组(Sed-TrkB/Fc组)及运动+TrkB/Fc组(TT-TrkB/Fc组)。于SCI术前1周进行L3-4鞘内置管。置管1周后使用改良Allen法制作T10不完全性SCI模型。于SCI术后第7天植入渗透压泵,并在Sed-PBS组和TT-PBS组的渗透压泵中灌入0.01M PBS,Sed-TrkB/Fc组和TT-TrkB/Fc组的渗透压泵中灌入TrkB阻滞剂(TrkB/Fc)。SCI后第8天,对TT-PBS组和TT-TrkB/Fc组进行减重平板训练。术后第1天、3天、7天、14天、21天、28天和35天进行BBB评分。实验结束后取材,使用Western Blot和免疫组化染色技术分析检测突触后膜密度蛋白-95(postsynaptic density protein-95,PSD-95)及突触素(synaptophysin,SYP)表达情况。 结果:术后14天,TT-PBS组BBB评分明显高于其他3组(P<0.05);术后21—35天,TT-PBS组BBB评分显著高于其他3组(P<0.001);术后28—35天,TT-TrkB/Fc组BBB评分高于Sed-PBS组及Sed-TrkB/Fc组(P<0.05)。蛋白免疫印迹结果显示,TT-PBS组PSD-95及SYP相对蛋白表达量显著高于其他3组(P<0.001);TT-TrkB/Fc组PSD-95及SYP相对蛋白表达量多于Sed-PBS组和Sed-TrkB/Fc组(P<0.05)。免疫组化结果显示,与Sed-PBS组、Sed-TrkB/Fc组和TT-TrkB/Fc组相比,TT-PBS组的PSD-95相对蛋白密度明显增高(P<0.01、P<0.001、P<0.01),且SYP相对蛋白密度也明显增高(P<0.001);TT-TrkB/Fc组的PSD-95及SYP相对蛋白密度也高于Sed-TrkB/Fc组及Sed-PBS组(P<0.05)。 结论:阻断BDNF-TrkB信号通路可明显抑制运动训练对不完全性SCI大鼠运动功能恢复和腰髓突触标记蛋白表达的促进作用。
关键词:脊髓损伤  运动训练  脑源性神经营养因子  运动功能  突触可塑性
Effects of exercise training on functional recovery after blocking BDNF-TrkB pathway in rat with spinal cord injury    Download Fulltext
The First Clinical Medical College of Nanjing Medical University, Nanjing, 210029
Fund Project:
Abstract:
      Abstract Objective:To investigate the effect of exercise training on locomotor function recovery and synaptic regeneration after blocking of brain-derived neurotrophic factor(BDNF) - Tyrosine kinase receptor B (TrkB) signaling pathway in rat with incomplete spinal cord injury (SCI). Method:Totally 32 female SD rats were randomly divided into 4 groups: injury+PBS group (Sed-PBS group), exercise+PBS group (TT-PBS group), injury+TrkB/Fc group (Sed-TrkB/Fc group) and exercise+TrkB/Fc group (TT-TrkB/Fc group). Intrathecal catheterization was operated in 1 week before SCI operation. After 1 weeks of intrathecal catheterization, T10 incomplete SCI model was made by modified Allen 's method. After 7 days of SCI, the Alzet osmotic pump was implanted into all SCI rats. The Alzet osmotic pump of Sed-PBS group and TT-PBS group were filled with 0.01M PBS, while Sed-TrkB/Fc group and TT-TrkB/Fc group with TrkB blocker (TrkB/Fc). After 8 days of SCI, the TT-PBS group and TT-TrkB/Fc group were underwent body-weight support treadmill training. The BBB score was performed at 1, 3, 7, 14, 21, 28 and 35 day after SCI. The lumbar spinal cord of all rats were removed at the end of this experiment. The Western Blot and immunohistochemical staining technique were used to detect the expression of postsynaptic density protein-95 (PSD-95) and synaptophysin (SYP). Result:Fourteen days after SCI, the BBB scores of TT-PBS group were higher than the other 3 groups (P<0.05), and 21-35 days after SCI, the BBB scores of TT-PBS group were significantly higher than the other 3 groups (P<0.001). However, 28-35 days after SCI, the BBB scores of TT-TrkB/Fc group was higher than Sed-PBS group and Sed-TrkB/Fc group (P<0.05). The Western blot results showed that the relative expression of PSD-95 and SYP protein in TT-PBS group were significantly higher than the other 3 groups (P<0.001), the protein of PSD-95 and SYP in TT-TrkB/Fc group was higher than Sed-PBS group and Sed-TrkB/Fc group (P<0.05). The immunohistochemistry results showed that, compared with Sed-PBS group, Sed-TrkB/Fc group and TT-TrkB/Fc group, the PSD-95 and SYP relative density in TT-PBS group were significantly higher (PSD-95, P<0.01, P<0.001, P<0.01, SYP, P<0.001), the relative protein density of PSD-95 and SYP in TT-TrkB/Fc group were higher than Sed-TrkB/Fc group and Sed-PBS group (P<0.05). Conclusion:Blocking the BDNF-TrkB signaling pathway can significantly inhibit the effect of exercise training on the recovery of locomotor function and the protein expression of lumbar spinal cord synapse in incomplete SCI rats.
Keywords:spinal cord injury  exercise training  brain-derived neurotrophic factor  locomotor function  synaptic plasticity
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