摘要
目的探索原肌球蛋白相关激酶B受体(TrkB)表达和TrkB信号通路活性在低频重复经颅磁刺激(rTMS)治疗癫痫大鼠过程中的变化以及作用机制。方法构建匹罗卡品诱导的癫痫大鼠模型,采用低频rTMS(1 Hz)干预癫痫大鼠模型后,Western Blot检测TrkB受体全长型和截短型蛋白表达以及全长型TrkB信号通路磷酸化水平的变化情况;膜片钳检测神经元自发放电频率的变化情况。结果经匹罗卡品诱导构建的癫痫大鼠模型,其神经元放电频率较对照组明显增加(P <0.05)。与对照组相比,癫痫模型中全长型TrkB受体表达降低(P <0.05),而截短型表达升高(P <0.05),此外全长型TrkB受体磷酸化程度降低(P <0.05)。低频rTMS干预癫痫模型后,与癫痫组相比,全长型TrkB受体表达上调(P <0.05),截短型TrkB受体表达下调(P <0.05),全长型TrkB受体磷酸化水平上调并激活TrkB信号通路(P <0.05)。最终,癫痫模型经低频rTMS干预后,其自发放电频率明显降低(P <0.05)。结论低频rTMS可能是通过上调癫痫模型中低表达的全长型TrkB受体,下调高表达的截短型TrkB受体,并激活全长型TrkB信号通路,最终发挥其抗癫痫作用。
Objective To explore the expression changes and effects of tropomyosin-related kinase B receptor(TrkB)and TrkB signalingin the treatment of epileptic rats by low frequency repetitive transcranial magnetic stimulation(rTMS). Methods Pilocarpine-induced status epilepticus rat model were constructed. After the intervention of low frequency rTMS(1 Hz)in epileptic rats,the changes in the expression of full-length and truncated TrkB receptor and the phosphorylation of the full-length TrkB signaling were detected by Western blot,then the changes in spontaneous discharge frequency of neurons were detected by patch clamp. Results The discharge frequency of neurons in pilocarpine-induced status epilepticus rat model was significantly higher than that of the control group(P < 0.05). Compared with the control group,the expression of the full-length TrkB was decreased(P < 0.05)and the truncated TrkB was increased(P < 0.05)in the epileptic model. Furthermore,the phosphorylation of full-length TrkB was decreased(P < 0.05). After the intervention of low frequency rTMS in epileptic rats,compared with the epileptic group,the full-length TrkB was upregulated(P < 0.05)and truncated TrkB was downregulated(P < 0.05),and the TrkB signaling was activated by the increase of the phosphorylation of full-length TrkB receptor(P < 0.05). Finally,the discharge frequency of neurons in epileptic models was decreased significantly after low frequency rTMS(P < 0.05). Conclusion Low frequency rTMS might upregulate the expression of full-length TrkB receptor,downregulate the truncated TrkB receptor and activate the full length TrkB signaling in the epileptic model to exertanti-epileptic effect.
作者
付翁
杨锦
齐琦
王明阳
谢伟
FU Weng;YANG Jin;QI Qi;WANG Mingyang;XIE Wei(Biomedicine Research Center,Basic Medical College and Baotou Medical College of Neuroscience Institute,Baotou Medical College,Baotou 014040,China)
出处
《实用医学杂志》
CAS
北大核心
2019年第12期1905-1909,共5页
The Journal of Practical Medicine
基金
国家自然科学基金项目(编号:31860307)
内蒙古自治区高等学校“青年科技英才支持计划”项目(编号:NJYT-18-B26)
包头医学院科学研究基金项目(编号:BYJJ-YF 201606)
内蒙古自治区大学生创新创业训练计划项目(编号:201710127001,201710127009,201810130006)
包头医学院花蕾计划项目(编号:2017BYJJ-HL-01,2017BYJJ-HL-09)
关键词
低频重复经颅磁刺激
癫痫
TrkB受体
信号通路
大鼠
low frequency repetitive transcranial magnetic stimulation
epilepsy
TrkB receptor
signaling pathway
rat
