深部脑磁刺激对帕金森病模型大鼠运动症状治疗的安全性评价

Safety evaluation during deep-brain magnetic stimulation (DMS) treating motor symptoms in Parkinsonian rats

目的评估深部脑磁刺激(deep-brain magnetic stimulation,DMS)对单侧帕金森病(Parkinson's disease,PD)模型大鼠运动障碍的治疗作用及DMS治疗的安全性。方法立体定位注射六羟基多巴胺(6-hydroxydopamine,6-OHDA)于大鼠右侧纹状体制备单侧帕金森病模型,假手术对照组(Sham组)依据同样方法注射0.9%(质量分数)氯化钠注射液。利用阿扑吗啡筛选模型后,造模成功的动物采用均衡随机化分组的方式分为模型对照组(Model组)、δ节律DMS治疗组(DMS-δ组)、γ节律DMS治疗组(DMS-γ组),其中两种DMS治疗组行每天40 min、持续4周的DMS治疗。通过碰壁实验检测大鼠运动行为,通过大鼠体质量的测定、外周血淋巴细胞的分类及计数、主要组织器官的苏木精-伊红(Hematoxylin-Eosin staining,HE)染色评价DMS治疗的安全性。结果 (1)检测大鼠运动行为显示,DMS-γ治疗组损伤侧的肢体利用率显著高于Model组,差异具有统计学意义(P<0.05),而DMS-δ组相较于Model组差异无统计学意义(P>0.05)。(2)Sham组、Model组、DMS-δ组、DMS-γ组大鼠体质量差异均无统计学意义(P>0.05)。(3)Sham组、Model组、DMS-δ组、DMS-γ组大鼠外周血总淋巴细胞与T细胞的数量和比例差异均无统计学意义(P>0.05)。DMS-δ组大鼠的自然杀伤(natural killer,NK)细胞数量和比例相较于Model组有显著改善。(4)HE染色显示,DMS对大鼠主要器官包括心、肝、脾、肺、肾、胃、小肠、睾丸均未造成明显的组织病理变化。结论 DMS-γ治疗可改善PD大鼠双侧肢体不对称性运动障碍,且DMS对PD大鼠运动行为的治疗中无明显不良反应,表明DMS在对PD大鼠运动症状的治疗中具有很好的安全性。

Objective To explore the security via DMS to treat motor symptoms in hemi-parkinsonian rats.Methods Rats were injected with 6-hydroxydopamine （6-OHDA） into right striatum to establish unilateral parkinsonian model.Sham group received the same volume of normal saline by the same procedure.After screened via apomorphine,the successful parkinsonian rats were randomly grouped into model,δ rhythm DMS treatment （DMS-δ） and γ rhythm DMS treatment （DMS-γ）.Among each DMS treatment group,40 minutes trains of DMS were administered daily for 4 weeks.Cylinder tests were conducted to detect motor outcomes.Body weight determination,peripheral blood lymphocytes classification ＆amp; counting,HE staining were executed to evaluate the security of DMS.Results ①The lesioned side forelimb usage ratio in Sham and DMS-γ groups were significantly higher than that in Model group.②There was no significant difference of body weight between each group,indicating that DMS had no significant effects on body weight.③There was no significant difference of the number and percentage of total lymphocytes ＆ T cells between each group,while the natural killer （NK） cells number and percentage in DMS-δ group were significantly higher than that in Model group.④Results of HE staining for major organs showed no significant histopathological change.Conclusion DMS-γ treatment alleviated bilateral limb asymmetry in PD rats.Meanwhile,DMS treatment showed no significant side effects,indicating that DMS showed satisfactory security in the treatment of motor symptoms in PD rats.