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目的研究低频重复经颅磁刺激对难治性颢叶癫癎大鼠的治疗作用,以及对海马脑源性神经营养因子(BDNF)和神经肽Y(NPY)表达水平的影响,以探讨低频重复经颅磁刺激治疗癫癎的可能机制。方法于海马CA3区注射海仁酸制备难治性颞叶癫癎大鼠模型,以低频重复经颅磁刺激方法共治疗10 d(连续治疗5 d、间隔2 d,治疗2周)。分别观察不同处理组大鼠治疗前后海马区脑电图变化及尖波数目;免疫组织化学染色检测手术后第3周时海马CA3区BDNF和NPY表达变化。结果与治疗前尖波数目(T_3:16.16±1.17,T_4:14.94±0.98)比较,低频重复经颅磁刺激治疗后难治性颞叶癫癎大鼠脑电图尖波数目(T_3:9.09±0.67,T_4:8.93±0.91)明显减少(均p=0.000);海马CA3区BDNF(治疗前后IOD值:49 571.40±2344.02比29 602.07±1932.82)、酪氨酸蛋白激酶B(TrkB,治疗前后IOD值:2946.77±1142.79比18 104.34±934.58)和NPY(治疗前后IOD值:33 823.05±843.45比15 037.14±772.95)阳性细胞数目明显减少(均P=0.000)。结论低频重复经颅磁刺激可以通过降低难治性颞叶癫癎大鼠癎样放电,以及下调海马BDNF、TrkB和NPY表达水平而发挥抗癫癎作用。
Objective To investigate the therapeutic effect of low frequency repetitive transcranial magnetic stimulation on intractable epileptic hippocampal epilepsy rats and its effect on the expression of brain-derived neurotrophic factor (BDNF) and neuropeptide Y (NPY) Transcranial magnetic stimulation of epilepsy possible mechanism. Methods A rat model of intractable temporal lobe epilepsy was prepared by injecting meric acid into hippocampal CA3 area. The rats were treated with low-frequency repetitive transcranial magnetic stimulation for 10 days (continuous treatment for 5 days, interval 2 days for 2 weeks). The changes of electroencephalogram (EEG) and the number of spikes in hippocampus were observed before and after treatment in different groups. The expression of BDNF and NPY in hippocampal CA3 area were detected by immunohistochemical staining. Results Compared with the number of spikes before treatment (T_3: 16.16 ± 1.17, T_4: 14.94 ± 0.98), the number of tine wave of electroencephalogram in refractory temporal lobe epileptic rats after low frequency repetitive transcranial magnetic stimulation (T_3: 9.09 ± 0.67, T_4: 8.93 ± 0.91) (all p = 0.000); BDNF in hippocampal CA3 area (IOD before and after treatment: 49 571.40 ± 2344.02 vs. 29 602.07 ± 1932.82), tyrosine kinase B (TrkB, Values: 2946.77 ± 1142.79 vs. 18 104.34 ± 934.58) and NPY (IOD before and after treatment: 33 823.05 ± 843.45 vs 15 037.14 ± 772.95) were significantly decreased (all P = 0.000). Conclusion Low-frequency repetitive transcranial magnetic stimulation can exert antiepileptic effect by reducing the hippocampal discharge in refractory temporal lobe epileptic rats and down-regulating the expression of BDNF, TrkB and NPY in the hippocampus.