重复经颅磁刺激对帕金森模型小鼠纹状体VMAT-2和SYN表达的影响

Effect of repetitive transcranial magnetic stimulation on vesicular monoamine transporter-2 and synaptophysin expressions in striatum of Parkinson's disease model mice

目的探讨重复经颅磁刺激(repetitive transcranial magnetic,rTMS)对帕金森病(Parkinson’sdisease,PD)模型鼠纹状体多巴胺(dopamine,DA)含量及Ⅱ型单胺囊泡转运体(vesicular monoamine transporter-2,VMAT-2)和突触体素(synaptophysin,SYN)表达的影响。方法65只雄性C57BL/6J小鼠随机分为:对照组、PD模型组、假磁刺激组、rTMS-1组、rTMS-2组,每组13只。小鼠皮下注射MPTP(15mg.kg-1,每小时注射1次,注射4次)复制帕金森病模型,重复经颅磁刺激干预,利用高效液相色谱-电化学(HPLC-ECD)测定纹状体DA含量;免疫组织化学染色检测VMAT-2和SYN的表达变化,并借助图像分析系统对其进行定量分析。结果rTMS-1组和rTMS-2组纹状体DA含量较对照组明显减少(P<0.01),但显著高于PD模型组和假磁刺激组(P<0.01);rTMS-1组和rTMS-2组纹状体VMAT-2和SYN表达均明显少于对照组且显著高于PD模型组和假磁刺激组,其免疫反应产物校正光密度值(COD)均显著低于对照组(P<0.05),并显著高于PD组和假磁刺激组(P<0.05),TMS-1组和rTMS-2组间无显著差异。结论rTMS可诱导PD鼠纹状体区DA释放增加,并使VMAT-2和SYN表达上调。

Objective To investigate the effect of repetitive transcranial magnetic stimulation （rTMS） on the contents of Dopamine and vesicular monoamine transporter-2 （VMAT-2） and synaptophysin （SYN） expressions in striatum of Parkinson＇ s disease （PD） model mice. Methods Sixty-five male C57BL/6J mice were randomly divided into 5 experimental groups： control group, PD model group, sham rTMS group, rTMS-1 group exposed to 110% motion threshold, rTMS-2 group exposed to 130% motion threshold, with 13 mice in each group. The model of Parkinsion＇ s disease of C57BL/6J mice were made by the subcutaneous injection of MPTP solution and then were treated with rTMSfor 14 days. The contents of Dopamine in the striatum were measured by high performance liquid chromatography （HPLC-ECD）. The VMAT-2 and SYN expressions in striatum were detected by immunohistochemistry and analysed quantitatively by image analysis system. Results The contents of Dopamine and the positive expressions of VMAT-2 and SYN in rTMS-1 and rTMS-2 groups were significantly lower than those in control group （ P 〈0.01 ）, but higher than those in PD and sham rTMS groups （ P 〈0.01 ）. The corrected optical density （COD） of immunoreactive products of VMAT-2 and SYN was lower than that of control group （ P 〈 0.05 ） and significantly higher than that of PD and sham rTMS groups （ P 〈 0.05 ）. There was no significant difference in COD between rTMS-1 and rTMS-2 groups. Conclusion rTMS can increase the release of Dopamine and the expressions of VMAT-2 and SYN in striatum of PD model mice, therefore we presume that rTMS may play a role in treating parkinson＇ s disease by increasing the expressions of VMAT-2 and SYN.