重复经颅磁刺激对脊髓损伤大鼠痉挛状态及BDNF-TrkB信号通路的影响  

Effects of repetitive transcranial magnetic stimulation on spasticity and BDNF-TrkB signaling pathway in rats with spinal cord injury

作　　者：魏修盼 陈沫 周静[1,2] 刘雅丽 WEI Xiupan;CHEN Mo;ZHOU Jing(Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030)

机构地区：[1]华中科技大学同济医学院附属同济医院康复医学科,武汉市430030 [2]湖北省中西医结合医院康复医学中心

出　　处：《中国康复医学杂志》2024年第7期926-933,共8页Chinese Journal of Rehabilitation Medicine

基　　金：国家自然科学基金面上类项目(2018CFB587)。

摘　　要：目的:探讨重复经颅磁刺激(rTMS)对脊髓损伤(SCI)大鼠痉挛状态的影响,探讨rTMS对痉挛的作用与脑源性神经营养因子(BDNF)-酪氨酸激酶受体B(TrkB)信号通路的关系。方法:研究分为A、B、C三部分。分别有18只、30只、15只雌性SD大鼠,共63只。A、B部分的大鼠均随机分为假手术组(Sham组)、SCI组和SCI+rTMS组。C部分的大鼠随机分为SCI组、SCI+rTMS组、SCI+rTMS+K252a组。SCI制模1周后对rTMS治疗组进行为期4周的干预。A部分每组大鼠干预前后使用H反射(H_(max)/M_(max)比值)评估大鼠后肢的痉挛状态,BBB评分连续每周评估运动功能。B部分在实验结束后采用Western Blot和免疫荧光检测各组大鼠皮质、脊髓损伤临近部位以及腰骶部BDNF、TrkB和KCC2的表达。C部分在SCI制模后1周,使用K252a阻断SCI+rTMS+K252a组的BDNF-TrkB信号通路,在4周rTMS治疗期间,用BBB评分评估大鼠后肢运动,实验结束后采用Western Blot检测KCC2的表达。结果:①A部分:SCI后2—5周,SCI+rTMS组BBB评分明显大于SCI组(P<0.05)。SCI后第5周,SCI+rTMS组痉挛大鼠H_(max)/M_(max)明显低于SCI组(P<0.05),两组大鼠RDD差异无显著性意义(P>0.05)。②B部分:Western Blot和免疫荧光显示,SCI 5周后,SCI+rTMS组皮质部位、脊髓损伤临近部位以及腰骶部脊髓BDNF、TrkB和KCC2的表达量较SCI组均明显增加(P<0.05)。③C部分:SCI后第2—5周,SCI+rTMS+K252a组BBB评分明显小于SCI+rTMS组(P<0.05)。Western Blot显示,SCI后第5周,SCI+rTMS+K252a组各部位KCC2的表达量明显小于SCI+rTMS组(P<0.05)。结论:rTMS可改善SCI大鼠的痉挛状态和运动功能,该过程与BDNF、TrkB和KCC2含量增加有关,rTMS缓解SCI后痉挛的机制可能与BDNF-TrkB-KCC2信号通路相关。Objective:To investigate the effects of repetitive transcranial magnetic stimulation(rTMS)on spasticity in rats with spinal cord injury(SCI)and explore the relationship between the effect of rTMS on spasticity and the signaling pathway of BDNF-TrkB.Method:This study was divided into three parts:A,B and C.There were 18,30 and 15 female SD rats in each part,respectively,and a total of 63 SD rats.Rats in Part A and Part B were randomly divided into Sham group,SCI group and SCI+rTMS group.Rats in Part C were randomly divided into SCI group,SCI+rT-MS group,and SCI+rTMS+K252a group.One week after the successful SCI modeling,rTMS treatment groups were given a 4-week intervention.In Part A,H reflex(H-_(max)/M-_(max)ratio)was used to evaluate the spasticity,and BBB score was used to evaluate the motor function every week.In Part B,Western Blot and immunofluorescence were used to detect the expressions of BDNF,TrkB and KCC2 in cortex,the adjacent parts of damage and lumbosacral spinal cord after the experiment.One week after SCI modeling,K252a was used to block the BDNF-TrkB signaling pathway in the SCI+rTMS+K252a group.During 4 weeks of rTMS treatment,BBB score was used to evaluate the hind limb motor function of the rats every week.After experiment,Western Blot was used to detect the expression of KCC2.Result:①Part A:BBB scores in the SCI+rTMS group were significantly higher than those in SCI group during 2—5 weeks after SCI(P<0.05).At the 5th week after SCI,H_(max)/M_(max)in the SCI+rTMS group was significantly lower than that in the SCI group(P<0.05),there was no significant difference in RDD between the two groups(P>0.05).②Part B:Western Blot results showed that 5 weeks after SCI,the expressions of BDNF,TrkB and KCC2 in the cortex,adjacent to the spinal cord injury and lumbosacral spinal cord in the SCI+rTMS group were significantly increased compared with the SCI group(P<0.05).③Part C:During 2—5 weeks after SCI,BBB scores in the SCI+rTMS+K252a group were significantly lower than the SCI+rTMS group(P<0.05).W

关 键 词：脊髓损伤 痉挛 重复经颅磁刺激 脑源性神经营养因子 

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