重复经颅磁刺激对阿尔茨海默病患者临床症状及血浆微小核糖核酸-125b、血浆磷酸化Tau-181蛋白的影响

关键词：重复经颅磁刺激  阿尔茨海默病  血浆微小核糖核酸-125b  血浆磷酸化Tau-181蛋白

Keywords:repetitive transcranial magnetic stimulation  Alzheimer's disease  microRNA-125b  phosphorylated Tau181 protein

摘要：

      摘要 目的：观察重复经颅磁刺激(repetitive transcranial magnetic stimulation， rTMS)对阿尔茨海默病(Alzheimer's disease， AD)患者认知功能、神经精神行为症状及血浆微小核糖核酸-125b（microRNA-125b， miR-125b）、血浆磷酸化Tau-181蛋白（phosphorylated Tau181 protein， P-tau181）表达的影响。 方法：筛选轻中度AD患者34例，随机分为对照组（n=16）和试验组（n=18）。对照组采取认知训练及重复经颅磁伪刺激，试验组采取认知训练结合重复经颅磁真刺激。磁刺激强度为100%的静息运动阈值，频率为10Hz，每日治疗1次，每周治疗5天，持续4周，刺激脑区为左侧前额叶背外侧区和左侧颞叶区。在治疗前、后进行Addenbrooke-Ⅲ认知检查（the Addenbrooke Ⅲ cognitive examination， ACE-Ⅲ）、简易精神状态量表（mini-mental state scale， MMSE）及神经精神症状问卷（neuropsychiatric inventory， NPI）评估，并采用实时荧光定量聚合酶链式反应（real-time fluorescence quantitative polymerase chain reaction， qRT-PCR）技术检测微小miR-125b表达量，酶联免疫吸附测定（enzyme-linked immunosorbent assay， ELISA）技术检测P-tau181的浓度。 结果：治疗结束后，试验组ACE-Ⅲ、MMSE和NPI评分以及miR-125b、P-tau181均较组内治疗前显著改善，差异具有显著性意义（P<0.05），且上述指标与对照组治疗后相比，差异具有显著性意义（P<0.05）；而对照组各项指标改善不具有显著性意义（P>0.05）。 结论：rTMS能改善轻中度AD患者的认知功能及神经精神行为症状，这可能与rTMS促进血浆miR-125b的表达和抑制P-tau181蛋白产生相关。

Abstract:

      Abstract Objective： To observe the effects of repetitive transcranial magnetic stimulation (rTMS) on cognitive function， neuropsychiatric behavioral symptoms， expression of plasma microRNA-125b (miR-125b) and phosphorylated Tau181 protein (P-Tau181) of patients with Alzheimer's disease (AD). Method： Thirty-four patients with mild to moderate AD were screened and randomly divided into control group (n=16) and experimental group (n=18). The control group received cognitive training and repetitive transcranial magnetic pseudo-stimulation， and the experimental group received cognitive training and repetitive transcranial magnetic real stimulation. The magnetic stimulation intensity was 100% resting movement threshold (RMT)， frequency was 10Hz. It's administered once a day， 5 days a week for 4 weeks. The stimulation site were the left dorsolateral prefrontal lobe and left temporal lobe. The Addenbrooke Ⅲ cognitive examination (ACE-Ⅲ)， mini-mental state scale (MMSE) and neuropsychiatric inventory (NPI) were evaluated before and after treatment. The microRNA-125b expression was detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) and the concentration of P-Tau181 was determined by enzyme-linked immunosorbent assay (ELISA). Result： After treatment， the scores of ACE-Ⅲ， MMSE and NPI， miR-125b and P-Tau181 in the experimental group were significantly improved compared with those before treatment(P<0.05). There was no improvement of all indexes in the control group(P>0.05). Conclusion： rTMS improve the cognitive function and neuropsychiatric symptoms of patients with mild to moderate AD， which may be related to the promotion of plasma miR-125b expression and inhibition of P-Tau181 protein production by rTMS. It is worthy for clinical application.