Abstract: Objective To observe the efficacy of the treatment of repetitive transcranial magnetic stimulation (rTMS) on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Methods Fifty-six C57BL/6J male mice were divided into 4 groups: PD model group, sham magnetic stimulation group (s-rTMS group), rTMS group and control group. Mice were given intraperitoneal injection of MPTP (15 mg/kg, every 2 h, 4 times) to prepare mouse model of Parkinson's disease 24 h before accepting repetitive transcranial magnetic stimulation. The stimulation were controlled at 1.00 Hz, 1.00 T, and lasted for 25 s, being performed at fixed time for 14 d. At the 1, 3, 7 and 14 d after MPTP injection, Rotarod Test were performed to evaluate physical coordination ability and freedom of movement of mice. Immunohistochemical staining was used in the midbrain and striatum to count the number of tyrosine hydroxylase (TH) -positive cells, and high-performance liquid chromatography-electrochemical detection (HPLC-ECD) of striatal dopamine content was applyed. Results The rotary number of mice in rTMS group（85.89±3.74）were significantly higher than that in PD group (59.71 ± 8.33; P = 0.000). TH-positive neurons of substantia nigra in rTMS group (36.67 ± 3.82) were significantly more than PD group (31.67 ± 3.35; P = 0.000). Dopamine concentration in striatum of PD group (152.35 ± 1.64) was significantly lower than that in rTMS group (258.70 ± 1.06; P = 0.000). Conclusion The repetitive transcranial magnetic stimulation could improve the motor coordination of MPTP mice and protect injured TH-positive neurons in substantia nigra and TH-positive nerve fibers in striatum, as well as elevating dopamine level in striatum.

Key words: Parkinson disease, 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, Transcranial magnetic stimulation, Tyrosine 3-monooxygenase, Dopamine, Immunohistochemistry, Disease models, animal

摘要： 目的 观察重复经颅磁刺激对MPTP 帕金森病模型小鼠的治疗效果。方法 于雄性C57BL/6J 小鼠皮下注射MPTP 制备帕金森病动物模型，24 h 后进行重复经颅磁刺激（刺激频率1.00 Hz、刺激强度1.00 T、刺激时间25 s/次，共刺激5 个序列，1 次/d）。Rotarod 实验评价小鼠身体协调能力和连续运动能力，免疫组织化学染色观察重复经颅磁刺激前后黑质区酪氨酸羟化酶阳性神经元数目和纹状体区酪氨酸羟化酶阳性神经纤维变化，高效液相色谱-电化学法检测重复经颅磁刺激对帕金森病小鼠纹状体多巴胺表达水平的影响。结果 重复经颅磁刺激组小鼠停留于旋转杆上的圈数（85.89 ± 3.74）、黑质区酪氨酸羟化酶阳性神经元数目（36.67 ± 3.82）和纹状体多巴胺表达水平（258.70 ± 1.06）均高于单纯帕金森病模型组（59.71 ± 8.33，31.67 ± 3.35，152.35 ± 1.64；均P = 0.000）。结论 重复经颅磁刺激可改善帕金森病小鼠运动协调能力，保护受损黑质区酪氨酸羟化酶阳性神经元及纹状体区酪氨酸羟化酶阳性神经纤维，提高纹状体多巴胺及其代谢产物水平。

关键词: 帕金森病, 1-甲基-4-苯基-1, 2, 3, 6-四氢吡啶, 经颅磁刺激, 酪氨酸单氧化酶, 多巴胺, 免疫组织化学, 疾病模型, 动物