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  被引量:5

Effects of exercise training on functional recovery after blocking BDNF-TrkB pathway in rat with spinal cord injury

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作  者:李向哲[1,2] 王红星 谢财忠 吴勤峰[2] 宋新建 曹雅娜[6] 方露 丁洁[1] 王彤 

机构地区:[1]南京医科大学第一临床医学院,南京210029 [2]苏州科技城医院康复医学中心 [3]南京医科大学第一附属医院康复中心 [4]南京军区南京总医院康复科 [5]南通市第二人民医院康复科 [6]江苏省中医院康复科

出  处:《中国康复医学杂志》2017年第12期1331-1337,1344,共8页Chinese Journal of Rehabilitation Medicine

基  金:国家自然科学基金面上项目(81171851)

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TTPBS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。Objective: To investigate the effect of exercise training on locomotor function recovery and synaptic regenera- tion 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 block- er (TrkB/Fc). After 8 days of SCI, the TT-PBS group and TT-TrkB/Fc group were underwent body-weight sup- port treadmill training. The BBB score was performed at 1, 3, 7, 14, 21, 28 and 35 day after SCI. The lum- bar spinal cord of all rats were removed at the end of this experiment. The Western Blot and immunohisto- chemical 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 S

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 

分 类 号:R651.2[医药卫生—外科学] R493[医药卫生—临床医学]

 

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