摘要
目的探讨重复经颅磁刺激（rTMS）对帕金森病（PD）小鼠黑质多巴胺能神经元及胶质源性神经营养因子（GDNF）的影响。方法32只雄性C57BL／6J小鼠随机分为生理盐水组、模型组、假刺激组及磁刺激组，每组8只。采用1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）皮下注射，每次15mg／kg体重，连续注射4次，每次间隔2h，建立急性PD小鼠模型。磁刺激组小鼠每天接受1Hz、1T的磁刺激治疗（共5个序列，25脉冲／序列），疗程为2周。经rTMS干预后，通过免疫组织化学技术检测黑质酪氨酸羟化酶（TH）和GDNF的表达变化，并借助图像分析系统进行定量分析。结果模型组、假刺激组TH免疫阳性（TH-ir）和GDNF免疫阳性（GDNF-ir）细胞计数、校正光密度（COD）值较生理盐水组减少（P〈0．01）；磁刺激组TH-ir和GDNF-ir细胞计数、COD值均较模型组和假刺激组增加（P〈0．05）。相关分析显示黑质区TH-ir和GDNF-ir细胞计数呈明显正相关（r=0．836，P〈0．01），相应的COD值比较亦呈明显正相关（r=0．921，P〈0．01）。结论rTMS明显增加PD小鼠黑质TH-ir细胞数量和COD值，推测其对黑质多巴胺能神经元具有保护作用，而上调黑质区GDNF的表达可能是其作用机制。
Objective To investigate the effect and its underlying mechanism of repetitive transcranial magnetic stimulation （rTMS） on dopaminergic neurons and glial cell line-derived neurotrophic factor （GDNF） in the substantia nigra （SN） in mice with Parkinson＇s disease （PD）. Methods Thirty-two male C57BL/6J mice were randomly divided into a normal saline group, a sham-rTMS group, a PD model group and an rTMS group, with 8 mice in each group. All the miee except those in the normal saline group were administered with 4 times of subcutaneous injection of 1-methyl, 4-phenyl-1, 2, 3, 6 tetrahydropyridine （MPTP） 15 mg/kg at 2-hour intervals in I day to induce neuronal injury in the SN and to establish acute mice PD model. The mice in the rTMS group received 5 trains of 1 Hz rTMS for 25 s, at the intensity of 1 Tesla （T） daily for 2 weeks. After rTMS, the effect of rTMS on PD mice was observed by immunohistoehemieal technique with regard to the expression of tyrosine hydroxylase （TH） and GDNF in the SN, and the quantitative analysis was performed by an advanced image-analysis system. Results Compared with normal saline group, the number of TH and GDNF immunoreaetive （ TH-ir and GDNF-ir） cells and the corrected optical density （COD） values of PD model group and sham-rTMS group were significantly lower （P 〈 0.01 ） ;Compared with PD model and sham-rTMS groups, the numbers of TH and GDNF positive cells and COD values in rTMS group were significantly higher （ P 〈 0.05 ）. There was a significant positive correlation between the count of TH-ir and that of GDNF-ir cells （ r = 0,836, P 〈 0.01 ）. The correlation between the COD values of TH-ir and that of GD- NF-ir cells was also significant （r =0. 921 ,P 〈 0.01 ）. Conclusion rTMS markedly increased the number and the COD values of TH-positive dopaminergie neurons and simultaneously increased the number and the COD value of GDNF-ir cells in the SN of PD mice. These findings suggest that rTMS has neuroproteetive effects on dopaminergie neurons in the MPTP-indueed PD mice, which might be mediated by up-regulation of the expression of GDNF protein in the SN.
出处
《中华物理医学与康复杂志》
CAS
CSCD
北大核心
2008年第4期227-230,共4页
Chinese Journal of Physical Medicine and Rehabilitation
基金
河北省自然科学基金项目（C2007000842）
关键词
重复经颅磁刺激
帕金森病
黑质
酪氨酸羟化酶
胶质源性神经营养因子
Repetitive transcranial magnetic stimulation
Parkinson＇s disease
Substantia nigra
Tyrosine hydroxylase
Glial cell line-derived neurotrophic factor
