高频重复经颅磁刺激改善全脑缺血大鼠学习记忆及机制研究  

High frequency repeated transcranial magnetic stimulation improves learning and memory of global cerebral ischemia rats and its mechanism

作　　者：任丽君[1] 吴碧华[1] 刘黎明[1] 张梅 杨兴 Ren Lijun;Wu Bihua;Liu Liming;Zhang Mei;Yang Xing(Department of Geriatrics,Affiliated Hospital of North Sichuan Medical College,Nanchong,Sichuan 637000,China)

机构地区：[1]川北医学院附属医院老年科,四川南充637000

出　　处：《中华神经科杂志》2019年第7期537-542,共6页Chinese Journal of Neurology

摘　　要：目的研究高频重复经颅磁刺激(rTMS)对全脑缺血大鼠学习记忆的影响并探讨其机制。方法将体重210~250g的35只雄性SD大鼠(8~10周龄)按随机区组法随机分为假手术组(8只)、模型组(9只)、rTMS组(9只)、假刺激组(9只),采用改良四血管阻断法制作全脑缺血大鼠模型,其中rTMS组给予连续2周的10HzrTMS刺激,假刺激组给予假刺激。利用Morris水迷宫检测大鼠空间学习记忆能力,多通道在体记录技术采集海马CA1区局部场电位(local field potentials,LFPs)分析θ和γ节律振荡,免疫组织化学和蛋白免疫印迹法检测海马组织蛋白激酶A(PKA)、磷酸化环磷腺苷效应元件结合蛋白(p-CREB)表达。结果模型组与假手术组相比,平均逃避潜伏期延长[(35.16±0.80)s与(16.57±0.74)s,k=3.723,P=0.013]、跨越平台次数减少[(1.14±0.42)次与(4.46±0.23)次,k=3.185,P=0.042]以及原平台象限游泳时间缩短[(14.46±0.73)s与(29.31±0.42)s,k=3.027,P=0.047],海马CA1区LFPsθ和γ功率谱密度均值降低[分别为(-68.48±2.61)Hz与(-59.38±2.25)Hz,k=2.958,P=0.048;(-82.23±4.60)Hz与(-70.50±4.25)Hz,k=3.729,P=0.021],免疫组织化学染色显示海马PKA、p-CREB表达减少(分别为7184.26±975.12与25137.35±1010.62,k=3.588,P=0.027;1803.73±336.18与20175.25±727.23,k=2.912,P=0.049);rTMS组与模型组相比,平均逃避潜伏期缩短[(24.69±1.01)s与(35.16±0.80)s,k=4.082,P=0.034]、跨越平台次数增加[(2.42±0.31)次与(1.14±0.42)次,t=3.296,P=0.039]及原平台象限游泳时间延长[(23.07±0.67)s与(14.46±0.73)s,k=4.323,P=0.012],海马CA1区LFPsθ和γ功率谱密度均值升高[分别为(-63.81±3.12)Hz与(-68.48±2.61)Hz,k=3.582,P=0.015;(-75.80±4.58)Hz与(-82.23±4.60)Hz,k=4.051,P=0.026],免疫组织化学染色显示海马PKA、p-CREB表达增加(分别为13065.32±1045.18与7184.26±975.12,k=3.923,P=0.031;11032.83±562.86与1803.73±336.18,k=3.178,P=0.038)。结论高频rTMS可能通过增强海马CA1区θ和γ振荡和提高海马PKA、p-CREB蛋白表达,Objective To study the effect of high frequency repeated transcranial magnetic stimulation (rTMS) on learning and memory in rats with global cerebral ischemia and to investigate its mechanism. Methods Thirty-five male Sprague-Dawley rats (8-10 weeks old) were randomly divided into sham operation group (n=8), model group (n=9), sham-rTMS (s-rTMS) group (n=9) and rTMS group (n=9). The global cerebral ischemia model was established by modified four-vessel occlusion method. The rTMS group received 10 Hz rTMS stimulation for two weeks, whereas the s-rTMS group received sham stimulation. Morris water maze test was used to detect the spatial learning ability, multi-channel recording technique was used to detect the local field potentials in the hippocampus CA1 region of theta and gamma oscillation, and immunohistochemical staining and Western blotting were used to detect the expression of protein kinase A (PKA) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) of hippocampus. Results The average escape latency in the model group was longer than that in the sham operation group ((35.16±0.80) s vs (16.57±0.74) s, k=3.723, P=0.013), the spanning platform times and the original platform quadrant swimming time in the model group were shorter than that in the sham operation group (1.14±0.42 vs 4.46±0.23, k=3.185, P=0.042;(14.46±0.73) s vs (29.31±0.42) s, k=3.027, P=0.047). Compared with the sham operation group, the mean power spectral density of theta and gamma reduced ((-68.48±2.61) Hz vs (-59.38±2.25) Hz, k=2.958, P=0.048;(-82.23±4.60) Hz vs (-70.50±4.25) Hz, k=3.729, P=0.021), and the expression of PKA and p-CREB protein decreased in the model group (7 184.26±975.12 vs 25 137.35±1 010.62, k=3.588, P=0.027;1 803.73±336.18 vs 20 175.25±727.23, k=2.912, P=0.049). The average escape latency in the rTMS group was shorter than that in the model group ((24.69±1.01) s vs (35.16±0.80) s, k=4.082, P=0.034), and the spanning platform times and the original platform quadrant s

关 键 词：脑缺血 学习记忆 重复经颅磁刺激 蛋白激酶A 环磷腺苷效应元件结合蛋白 局部场电位 

分 类 号：R743[医药卫生—神经病学与精神病学]