成对关联刺激对脑梗死大鼠突触可塑性和神经元凋亡及脑源性神经营养因子的影响  

Effects of paired associative stimulation on synaptic ultrastructure, neuron apoptosis and BDNF in rats with cerebral infarct

作　　者：张香玉 胡艳 郭铁成 鲁银山 张秀娟张松 Zhang Xiangyu;Hu Yan;Guo Tiecheng;Lu Yinshan;Zhang Xiujuan;Zhang Song(Department of Rehabilitation Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Rehabilitation Medicine,the 5th Hospital of Zhengzhou University,Zhengzhou 470000,China;Department of Rehabilitation Medicine,Zhongnan Hospital,Wuhan University,Wuhan 430071,China;Department of Rehabilitation Medicine,Renmin Hospital,Wuhan University,Wuhan 430060,China)

机构地区：[1]华中科技大学同济医学院附属同济医院康复医学科,武汉430030 [2]郑州大学第五附属医院肌肉骨骼疼痛康复科 [3]武汉大学中南医院康复医学科 [4]武汉大学人民医院康复医学科

出　　处：《中华物理医学与康复杂志》2019年第11期812-817,共6页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：国家自然科学基金面上项目(81272156)。

摘　　要：目的观察成对关联刺激(PAS)对缺血性脑梗死大鼠缺血半暗带皮质突触超微结构、神经元凋亡的影响,并探讨其可能作用机制。方法健康雄性Sprague-Dawley大鼠45只,随机分为三组:假手术组、手术对照组及PAS组,每组15只。手术对照组和PAS组采用线栓法行右侧MCAO造模,假手术组行同样操作,但不栓塞大脑中动脉。造模成功后24 h,PAS组给予0.05 Hz、共90对脉冲的PAS干预,持续30 min,每天1次,连续28 d(周围神经电刺激强度为6 mA,波宽200μs;经颅磁刺激强度120%RMT),手术对照组及假手术组大鼠正常饲养但不给予任何干预。术后28 d取大鼠脑组织,采用透射电镜观察缺血半暗带皮质突触超微结构的变化、TUNEL法检测缺血半暗带皮质神经元凋亡情况、实时荧光定量PCR(RT-PCR)检测缺血半暗带皮质BDNF mRNA表达水平。结果①术后28 d,与假手术组相比,手术对照组和PAS组突触界面曲率、突触活性区长度及突触后膜致密物质厚度减小(P<0.05);与手术对照组相比,PAS组突触界面曲率、突触活性区长度及突触后膜致密物质厚度增加(P<0.05)。②术后28 d,与假手术组相比,手术对照组和PAS组皮质神经元凋亡比率明显增加(P<0.05);PAS组皮质神经元凋亡比率明显低于手术对照组(P<0.05)。③术后28 d,PAS组BDNF mRNA表达水平明显高于假手术组及手术对照组(P<0.05),手术对照组BDNF mRNA表达水平显著低于假手术组(P<0.05)。结论PAS可调节缺血性脑梗死大鼠神经可塑性、抑制神经元凋亡,而上调缺血半暗带皮质BDNF mRNA的表达水平可能是其作用机制之一。Objective To observe the effects of paired associative stimulation(PAS)on synaptic ultrastructure,neuron apoptosis and BDNF in rats with cerebral infarct,and explore the possible underlying mechanisms.Methods Forty-five male Sprague-Dawley rats were randomly divided into three groups:a sham operation group,a model group and a PAS group,with 15 rats in each.All the rats underwent a surgical operation for transient middle cerebral artery occlusion(MCAO)on the right side to model focal cerebral ischemia,with those in the sham operation group left without real occlusion.PAS treatment was given to rats in the PAS group 24h after MCAO model was successfully established,while no special intervention was given to those in the sham operation group and model group.After 28 days of treatment,transmission electron microscopy was used to investigate the ultrastructure of the ischemic penumbra,TUNEL was used to observe the apoptosis of cortex neurons,and real time-PCR to investigate BDNF mRNA expression.Results It was found that after 28 days treatment:①The synaptic curvature,the synapse length and the post-synaptic density(PSD)decreased significantly in the rats of model group in contrast to those of the sham control group(P<0.05).And compare to model group,the synaptic curvature,the synapse length and the PSD increased significantly in the rats of PAS group(P<0.05).②Compare to sham control group,the apoptosis rate of model group and PAS group increased significantly(P<0.05).And the apoptosis rate of PAS group decreased significantly in contrast to those of model group(P<0.05).③Compare to sham control group,BDNF mRNA expression of the PAS group increased significantly(P<0.05),while BDNF mRNA expression of the model group decreased significantly(P<0.05).BDNF mRNA expression of the PAS group increased significantly in contrast to those of model group(P<0.05).Conclusion PAS promotes neural plasticity and inhibits apoptosis of cortex neurons of the ischemic penumbra in rats with ischemic cerebral infarction.One of the under

关 键 词：成对关联刺激 突触超微结构 凋亡 脑源性神经营养因子 

分 类 号：R74[医药卫生—神经病学与精神病学]