目的 探讨高频重复经颅磁刺激(rTMS)对老年小鼠术后认知功能障碍(POCD)的影响,并分析其作用机制.方法 选择24只18月龄C57BL/6J雄性老年小鼠,采用随机数字表法分为对照组、手术组和rTMS组,每组8只.rTMS组术前连续10 d进行5 Hz rTMS真刺激,随后进行实验性剖腹手术,术后继续4 d rTMS真刺激,1次/d,磁刺激强度0.84 T,频率5 Hz,每个序列100脉冲,间歇时间30 s,重复10个序列,共1 000个脉冲.对照组和手术组术前连续10 d进行伪刺激,对照组不手术,手术组进行实验性剖腹手术,术后对照组和手术组接受4 d伪刺激.术后第3天采用旷场实验评估小鼠的运动能力(中心区域停留时间百分比、运动总距离和平均运动速度);术后第4天采用Y迷宫测试评估小鼠认知功能(进入新异臂次数百分比、新异臂停留时间百分比和新异臂移动总距离);采用Western blot法检测小鼠海马组织脑源性神经营养因子(BDNF)、原肌球蛋白相关激酶B(TrkB)和神经生长因子(NGF)蛋白表达水平.结果 ① 运动功能:3组旷场中心区域停留时间百分比、运动总距离和平均运动速度比较,差异均无统计学意义(P＞0.05).② 认知功能:3组小鼠探索新异臂次数百分比差异无统计学意义(P＞0.05);与对照组比较,手术组新异臂停留时间百分比、新异臂移动总距离均明显降低,差异均具有统计学意义(P＜0.05);与手术组比较,rTMS组新异臂停留时间百分比、新异臂移动总距离均明显升高,差异均具有统计学意义(P＜0.05).③ 海马组织蛋白表达水平:与对照组比较,手术组海马组织中BDNF、TrkB和NGF蛋白表达水平均明显降低,差异均具有统计学意义(P＜0.05);与手术组比较,rTMS组海马组织中BDNF、TrkB和NGF蛋白表达水平均明显升高,差异均具有统计学意义(P＜0.05).结论 高频rTMS能改善老年小鼠POCD,其作用机制可能与rTMS激活BDNF/TrkB信号通路和增加NGF表达有关.
Effect of High Frequency Repetitive Transcranial Magnetic Stimulation on Aged Mice with Postoperative Cognitive Dysfunction Based on BDNF/TrkB Signaling Pathway
Objective To explore the effect and its mechanism of high frequency repetitive transcranial magnetic stimulation(rTMS)on aged mice with postoperative cognitive dysfunction(POCD).Methods A total of twenty-four 18-month-old C57BL/6J male aged mice were randomly divided into control group,operation group and rTMS group,with eight cases in each group.The rT-MS group received 5 Hz rTMS real stimulation for 10 consecutive days before operation,then underwent an experimental laparoto-my,and continued with another four days of rTMS real stimulation after operation,once a day,with a magnetic stimulation intensity of 0.84 T,frequency of 5 Hz,100 pulses per sequence,a 30-second interval time,10 repetitions for a total of 1 000 pulses.The con-trol group and the operation group received sham stimulation for 10 days before operation,the control group did not undergo the op-eration,while the operation group received experimental laparotomy,and then the control group and the operation group received sham stimulation for four days.Open field test was used to evaluate motor function(percentage of time spend in the central area,to-tal distance traveled,and average speed of movement)at the 3rd day after operation;Y-maze test was used to evaluate cognitive function(the percentage of entries into the novel arm,the percentage of time to stay in the novel arm and the total distance moved in the novel arm)at the 4th day after operation;Western blot was used to detect the protein expression levels of brain-derived neuro-trophic factor(BDNF),tropomyosin related kinase B(TrkB)and nerve growth factor(NGF)in the hippocampal tissue of the mice.Results(1)Motor function:there were no significant differences in the percentage of time spent in the central area of the open field,total distance traveled and average speed of movement among the three groups(P>0.05).(2)Cognitive function:there was no significant difference in the percentage of entries into the novel arm among the three groups(P>0.05);compared with the control group,the percentage of time spent in the novel arm and the total distance moved in the novel arm in the operation group de-creased significantly,and the differences were statistically significant(P<0.05).Compared with the operation group,the percentage of time spent in the novel arm and the total distance moved in the novel arm in the rTMS group increased significantly,and the dif-ferences were statistically significant(P<0.05).(3)Protein expression level of hippocampal tissue:compared with the control group,the protein expression levels of BDNF,TrkB and NGF in the hippocampal tissue in the operation group decreased significantly,and the differences were statistically significant(P<0.05).Compared with the operation group,the protein expression levels of BDNF,TrkB and NGF in the hippocampus in the rTMS group increased significantly,and the differences were statistically significant(P<0.05).Conclusion High frequency rTMS can improve POCD in aged mice,and its mechanism may be related to rTMS activating BDNF/TrkB signaling pathway and increasing NGF expression.
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