基于NMDA通路探讨茸菖胶囊干预月经性癫痫神经元模型的抗痫机制OA
Anti-epileptic mechanism of Rongchang Capsule intervention in the neuronal model of catamenial epilepsy was discussed based on the NMDA pathway
[目的]观察茸菖胶囊对月经性癫痫神经元模型的N-甲基-D-天冬氨酸(NMDA)受体的影响,探讨其作用机制.[方法]以外源性添加雌二醇(E2)的无镁诱导的癫痫神经元(月经性癫痫神经元模型)为研究对象,随机分为7组:对照组、癫痫模型组、月经性癫痫模型组、丙戊酸钠组、茸菖低剂量组、茸菖中剂量组和茸菖高剂量组.观察各组神经元形态、放电频率、静息膜电位、24 h NMDA电流变化、NMDA受体1(NR1)、NMDA受体2A(NR2A)蛋白表达情况.[结果]与对照组相比,月经性癫痫模型组高频高幅棘波放电明显增多、神经元数目明显减少,放电频率明显增加、静息膜电位明显升高、24 h NMDA通道电流密度明显增加(P<0.05或P<0.01),NR1蛋白表达明显降低、NR2A蛋白表达明显升高(P<0.05或P<0.01).与月经性癫痫模型组相比,丙戊酸钠组高频高幅棘波放电减少、神经元数目增多,放电频率明显减少(P<0.05),静息膜电位未见明显降低、24 h NMDA通道电流密度未见明显降低(P>0.05),NR1、NR2A蛋白表达未见明显改变(P>0.05);茸菖高剂量组高频高幅棘波放电明显减少、神经元数目明显增多,放电频率明显减少、静息膜电位明显降低、24 h NMDA通道电流密度明显降低(P<0.05),NR2A蛋白表达明显降低(P<0.05),NR1蛋白表达未见明显升高(P>0.05).[结论]茸菖胶囊可能通过下调NR2A蛋白表达,降低NMDA受体介导的神经的异常兴奋,从而减轻外源性添加E2的无镁癫痫神经元的异常放电,发挥抗癫痫作用.
[Objective]To observe the effect of Rongchang Capsules on N-Methyl-D-aspartic acid(NMDA)receptor in the neuronal model of catamenial epilepsy,and to explore its mechanism.[Methods]The magnesium-free epileptic neurons induced by exogenous E2(catamenial epileptic neuron model)were randomly divided into 7 groups:control group,epilepsy model group,catamenial epilepsy model group,sodium valproate group and Rongchang Capsules low dose group,Rongchang Capsules middle dose group and Rongchang Capsules high dose group.The neuronal morphology,discharge frequency,resting membrane potential,24 h NMDA current changes,NMDA Receptor 1(NR1)and NMDA Receptor 2A(NR2A)receptor protein expression were observed.[Results]Compared with the control group,the high-frequency and high-amplitude spike discharges in the catamenial epilepsy model group were significantly increased;the number of neurons was significantly decreased;the discharge frequency was significantly increased;the resting membrane potential was significantly increased;the 24 h NMDA channel current density was significantly increased(P<0.05 or P<0.01);the expression of NR1 protein was significantly decreased,and the expression of NR2A protein was significantly increased(P<0.05 or P<0.01).Compared with the catamenial epilepsy model group,the high-frequency high-amplitude spike wave discharge in the sodium valproate group was significantly decreased;the number of neurons increased;the discharge frequency decreased significantly(P<0.05);the resting membrane potential and the 24 h NMDA channel current density was not decreased significantly(P>0.05);the expression of NR1 and NR2A protein did not change significantly(P>0.05);the high-frequency and high-amplitude spike wave discharge in the Rongchang capsules high dose group was significantly decreased;the number of neurons was significantly increased;the discharge frequency was significantly decreased;the resting membrane potential was significantly decreased and the 24 h NMDA channel current density was significantly decreased(P<0.05),and the expression of NR2A protein was significantly decreased(P<0.05),and the expression of NR1 protein was not significantly increased(P>0.05).[Conclusion]Rongchang Capsules may reduce the abnormal excitability of NMDA receptor-mediated nerves by down-regulating the expression of NR2A protein,thereby reducing the abnormal discharge of magnesium-free epileptic neurons supplemented with exogenous E2,thus exerting anti-epileptic effects.
闫海虹;郭婷;陈海鹏;张喜莲;戎萍;李瑞本;付乾芳;马融
山西省儿童医院,太原 030013河南中医药大学第一附属医院,郑州 450003北京中医药大学东方医院,北京 100078天津中医药大学第一附属医院,天津 300381||中医国家临床医学研究中心,天津 300381天津中医药大学第一附属医院,天津 300381||中医国家临床医学研究中心,天津 300381天津中医药大学第一附属医院,天津 300381||中医国家临床医学研究中心,天津 300381天津中医药大学第一附属医院,天津 300381||中医国家临床医学研究中心,天津 300381天津中医药大学第一附属医院,天津 300381||中医国家临床医学研究中心,天津 300381
医药卫生
茸菖胶囊月经性癫痫神经元模型NMDA通路抗痫机制
Rongchang Capsulecatamenial epilepsyneuronal model of catamenial epilepticNMDA pathwayantiepileptic mechanism
《天津中医药》 2026 (2)
218-223,6
国家自然科学基金项目(81574018)山西省基础研究计划项目(202403021222477).
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