转化生长因子β_1降低大鼠自发性癫痫发作并抑制胶质细胞活化

Transforming growth factor beta 1 reduces spontaneous recurrent seizures and inhibits activation of glial cells in rats

目的:观察经鼻给予转化生长因子β1(TGF-β1)是否能减少匹罗卡品致痫大鼠慢性自发性癫痫的发作并探讨其可能机制。方法:经鼻给予大鼠重组人TGF-β1或等量PBS溶液,以匹罗卡品建立癫痫持续状态模型,癫痫持续状态后7 d经动态视频记录其活动,通过胶质纤维酸性蛋白(GFAP)和离子钙结合接头分子1(Iba1)免疫组化观察癫痫大鼠海马组织胶质细胞的活化,采用尼氏染色观察海马区神经元的死亡。结果:TGF-β1有效降低自发性癫痫的平均频率、发作程度和持续时间。癫痫持续状态后14 d TGF-β1治疗组海马区活化的胶质细胞明显少于匹罗卡品模型组(P<0.05);TGF-β1显著降低海马CA3区神经元的死亡(P<0.01)。结论:经鼻给予TGF-β1可降低大鼠自发重复性癫痫发作,抑制胶质细胞活化,从而减少神经元的死亡。

AIM： To investigate the mechanism that intranasal transforming growth factor beta 1 （TGF -β1 ） reduces the occurrence of spontaneous seizures after status epilepticus （SE） induced by pilocarpine. METHODS： The rats received recombinant human TGF - β1 or the same volume of PBS, and were treated with pilocarpine to induce SE. All the rats were put into a special cage for video monitoring 7 days later. The determinations of glial fibrillary acidic protein （GFAP） and ionized calcium - binding adaptor molecule 1 （ Iba1 ） positive cells by the method of immunohistochemistry were performed to evaluate the activation levels of the gliocytes in hippocampus. The neuron loss was measured by Nissl staining. RESULTS： TGF - β1 reduced the average frequency, severity and duration of spontaneous seizures. The activa- ted glia ceils in the hippocampus were significantly reduced in TGF - β1 group compared with pilocarpine group at 14 days after SE （P 〈0.05 ）. TGF -β1 significantly attenuated the loss of pyramidal neurons in hippocampal CA3 area at 14 days after SE （P 〈 0.01 ）. CONCLUSION： Intranasal TGF -β1 reduces spontaneous recurrent seizures by inhibiting the acti- vation of glia cells and attenuating the loss of pyramidal neurons.