经颅直流电刺激联合任务导向性康复训练对脊髓损伤大鼠前肢运动障碍的效果.pdf

https:/中国康复理论与实践 2023年7月第29卷第7期 Chin J Rehabil Theory Pract,Jul.,2023,Vol.29,No.7 经颅直流电刺激联合任务导向性康复训练对脊髓损伤大鼠前肢运动障碍的效果李芳1，霍速1，杜巨豹1，刘秀贞1，李小爽2，宋为群11.首都医科大学宣武医院康复医学科，北京市100053；2.北京中医药大学第三附属医院（密云院区）康复医学科，北京市 101599通信作者：宋为群，E-mail：基金项目：国家自然科学基金项目(No.82102659)摘要目的观察经颅直流电刺激(tDCS)联合任务导向性康复训练抓取单个小球(SPG)对C5单侧挫伤大鼠前肢运动功能的影响。方法60 只成年雄性 Sprague-Dawley 大鼠随机分为假手术组、脊髓损伤组、tDCS 组、SPG 组、假刺激组和tDCS+SPG组，每组各10只。假手术组仅摘除C5椎板，其余5组利用IH脊髓打击器制备C5半侧挫伤模型。造模后，tDCS 组给予 tDCS 治疗，SPG 组给予 SPG 治疗，假刺激组给予不通电流的 tDCS 治疗，tDCS+SPG组给予tDCS治疗和SPG治疗，脊髓损伤组和假手术组不给予任何治疗。术后4周，各组行Rearing实验、Grooming实验和运动诱发电位(MEP)检测。结果术后4周，与脊髓损伤组比较，tDCS组和tDCS+SPG组患侧前肢Rearing评分和Grooming评分升高(P 0.05)，tDCS+SPG组评分高于tDCS组和SPG组(P 0.05)，SPG组Grooming评分升高(P 0.05)；tDCS组、SPG 组和 tDCS+SPG 组 MEP振幅增加(P 0.05)，tDCS组和 tDCS+SPG 组潜伏期缩短(P 0.05)，tDCS+SPG组振幅明显高于tDCS组和SPG组(P 0.01)。结论tDCS能促进脊髓损伤大鼠运动功能的恢复，与任务导向性康复训练相结合效果更佳。关键词 脊髓损伤；经颅直流电刺激；任务导向性康复训练；运动功能；大鼠Effect of transcranial direct current stimulation combined with task-oriented rehabilitation training on forelimb motor dysfunction in rats with spinal cord injuryLI Fang1,HUO Su1,DU Jubao1,LIU Xiuzhen1,LI Xiaoshuang2,SONG Weiqun11.Department of Rehabilitation Medicine,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;2.Department of Rehabilitation Medicine,Beijing University of Chinese Medicine Third Affiliated Hospital(Miyun District),Beijing 101599,ChinaCorrespondence to SONG Weiqun,E-mail：Supported by National Natural Science Foundation of China(No.82102659)AbstractObjective To observe the effect of transcranial direct current stimulation(tDCS)combined with task-oriented rehabilitation training single pellet reaching and grasping(SPG)on the motor function of forelimb in rats with unilateral contusion of C5 spinal cord.Methods A total of 60 adult male Sprague-Dawley rats were randomly divided into sham operation group(sham group),spinal cord injury(SCI)group,tDCS group,SPG group,false group and tDCS+SPG group,with ten rats in each group.Only C5 lamina was removed in the sham group,and the C5 spinal cord contusion model was established by IH spinal cord impactor in the other five groups.The rats received tDCS in tDCS group,SPG in SPG group,DOI:10.3969/j.issn.10069771.2023.07.006 基础研究 作者简介：李芳(1990-)，女，汉族，山东临沂市人，博士，医师，主要研究方向：脊髓损伤的基础和临床研究。通信作者：宋为群(1965-)，女，布依族，贵州都匀市人，博士，主任医师，主要研究方向：神经康复。-777中国康复理论与实践 2023年7月第29卷第7期 Chin J Rehabil Theory Pract,Jul.,2023,Vol.29,No.7 https:/tDCS without current in false group,tDCS combined with SPG in tDCS+SPG group,and no treatment in the SCI and the sham groups.The rats were evaluated with Rearing and Grooming tests,and motor-evoked potential(MEP).Results Four weeks after operation,compared with SCI group,the scores of Rearing and Grooming increased in tDCS group and tDCS+SPG group(P 0.05),and they were more in the tDCS+SPG group than in tDCS group and SPG group(P 0.05);the score of Grooming increased in SPG group(P 0.05);while the amplitude of MEP increased in tDCS group,SPG group and tDCS+SPG group(P 0.05),and the latency shortened in tDCS group and tDCS+SPG group(P 0.05);and the amplitude increased more in tDCS+SPG group than in tDCS group and SPG group(P 0.05)。术后4周，与脊髓损伤组相比，tDCS组和tDCS+SPG组的Rearing评分升高(P 0.05)；tDCS+SPG 组的 Rearing 评分高于 tDCS 组和 SPG 组(P 0.05)。见表1。2.1.2 Grooming实验术前各组大鼠拟损伤侧前肢的 Grooming评分均为 5 分。术后 4 周，与脊髓损伤组相比，tDCS 组、表1各组Rearing实验患肢使用率比较 单位：%组别假手术组脊髓损伤组tDCS组SPG组假刺激组tDCS+SPG组F值P值n101010101010术前76.805.0175.706.8975.907.9176.207.2176.905.8474.206.990.2140.955术后4周76.705.1230.203.2241.103.32a36.203.1931.203.3050.602.68b,c,d242.410 0.001注：a.与脊髓损伤组比较，P 0.05；b.与脊髓损伤组比较，P 0.01；c.与tDCS组比较，P 0.05；d.与SPG组比较，P 0.05。-779中国康复理论与实践 2023年7月第29卷第7期 Chin J Rehabil Theory Pract,Jul.,2023,Vol.29,No.7 https:/SPG 组 和 tDCS+SPG 组 Grooming 评 分 均 增 加(P 0.05)；tDCS+SPG 组的 Grooming评分高于 tDCS组和SPG组(P 0.05)。见表2。2.2 MEP2.2.1 潜伏期与脊髓损伤组相比，tDCS组和tDCS+SPG组潜伏期缩短(P 0.05)。见表3。2.2.2 振幅与脊髓损伤组相比，tDCS 组、SPG 组和 tDCS+SPG组的MEP振幅均增大(P 0.05)；tDCS+SPG组的MEP 振 幅 明 显 大 于 tDCS 组 和 SPG 组(P 0.01)。见表3。3 讨论 脊髓损伤是一种中枢神经系统创伤性疾病，具有发病率高、死亡率高和致残性高的特点，目前缺乏有效的治疗方法，给患者、家庭和社会带来沉重负担11-12。大多数脊髓损伤发生在颈段脊髓，常见于C5，其次是C4和C69,13。挫伤是最常见的脊髓损伤类型14。tDCS以恒定微弱的直流电作用于大脑皮质，改变神经细胞跨膜电位，产生去极化或超极化现象，改变大脑皮质兴奋性，调控大脑功能15。tDCS具有极性特征和即刻效应，阳极刺激使神经元去极化，降低神经元产生动作电位的阈值，提高皮质兴奋性；阴极刺激使神经元超极化，提高神经元产生动作电位的阈值，降低皮质兴奋性15。tDCS除能调节刺激时的大脑皮质兴奋性，产生即刻效应，还能产生持久效应，后续效应可持续1 h16。tDCS可改善脊髓损伤后运动障碍，与常规/标准化康复训练相结合更具治疗潜力17-18。Cabral等8发现，在运动训练前进行 tDCS促进运动训练诱发可塑性的优化，其机制可能是脑刺激为随后的运动训练提供了皮质的兴奋性，优化了运动学习过程。因此，本研究先于脊髓损伤大鼠的M1区行阳极 tDCS 治疗 20 min，然后行 SPG 训练 30 min，结果表明该联合疗法较单独tDCS能更好改善脊髓损伤大鼠前肢运动功能。Rearing实验也称前肢不对称测试或前爪偏好测试，可用于评定中枢神经系统损伤导致的前肢不对称性功能障碍19-20。动物发生脊髓损伤后，在垂直触壁期间自发性使用患侧前肢的频率大幅度减少21。本研究发现，tDCS或tDCS联合SPG均能改善脊髓损伤大鼠患肢的自发性使用，且联合疗法更有利于脊髓损伤大鼠运动功能的恢复。Grooming 实 验 用 于 评 估 动 物 的 前 肢 修 饰 功能22-23。正常的梳理模式包括反复舔前爪，揉搓嘴巴和鼻子，然后到眼部区域和达头后部，最后前爪从耳后移至鼻子。在健康动物中，梳理模式对称，即先是一只前爪运动，随后另一只前爪做出相同运动20。本研究发现，脊髓损伤后几乎所有大鼠患侧梳理明显缺陷。无论单一tDCS或SPG治疗，还是tDCS联合SPG疗法均能明显提高脊髓损伤大鼠患侧前爪的Grooming评分，并且联合治疗的效果优于单一疗法。4 结论 tDCS促进脊髓损伤大鼠运动功能的恢复，联合运动康复训练效果更佳。其作用机制有待进一步研究。利益冲突声明：所有作者声明不存在利益冲突。表3各组术后4周MEP潜伏期和振幅比较组别假手术组脊髓损伤组tDCS组SPG组假刺激组tDCS+SPG组F值P值n101010101010潜伏期/ms7.180.189.200.278.090.42a8.900.459.050.367.770.38b52.440 0.001振幅/V49.842.196.371.3217.941.92b9.281.23a6.100.9339.553.63c,d,e816.341 0.001注：与脊髓损伤组比较，a.P 0.05；b.与脊髓损伤组比较，P 0.01；c.与脊髓损伤组比较，P 0.001；d.与 tDCS 组比较，P 0.01；e.与SPG组比较，P 0.001。表2各组Grooming评分比较组别假手术组脊髓损伤组tDCS组SPG组假刺激组tDCS+SPG组F值P值n101010101010术前5.000.005.000.005.000.005.000.005.000.005.000.00术后4周5.000.002.800.603.760.28a3.350.37b2.850.544.280.37c,d,e44.120 0.001注：a.与脊髓损伤组比较，P 0.05；b.与脊髓损伤组比较，P 0.01；c.与脊髓损伤组比较，P 0.001；d.与tDCS组比较，P 0.05；e.与SPG组比较，P 0.01。-780中国康复理论与实践 2023年7月第29卷第7期 Chin J Rehabil Theory Pract,Jul.,2023,Vol.29,No.7 https:/参考文献1 BACKUS D.Exploring the potential for neural recovery after incomplete tetraplegia through nonsurgical interventions J.PM R,2010,2(12 Suppl 2):S279-S285.2 WANG Y,LUO H,LIU Y,et al.Multimodal rehabilitation promotes axonal sprouting and functional recovery 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