Xiang Jun, Jiang Yugang
Department of Neurosurgery, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Int J Mol Sci. 2013 Dec 5;14(12):23751-61. doi: 10.3390/ijms141223751.
Our present study aimed to determine the antiepileptic activity of matrine, and explore the possible molecular mechanism. To evaluate the antiepileptic activity of matrine, seizures in mice induced by PTZ and MES were established, then the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests in mice were also carried out. For the molecular mechanism investigations, contents of aspartic acid (Asp), gamma-aminobutyric acid (GABA), glutamic acid (Glu), glycine (Gly) in seizures mice were determined; then, the chronic seizures rats induced by PTZ were prepared, and western blotting was used to determine the expressions of GAD 65, GABAA and GABAB in the brains. In the results, matrine showed significant antiepileptic effects on seizures mice induced by MES and PTZ. Moreover, the pentobarbital sodium-induced anaesthetizing time and locomotor activity tests were also demonstrated that matrine had obvious antiepileptic effects. Additionally, our results revealed that after treatment with matrine, contents of GABA can be elevated, and the contents of Glu were obviously decreased. Furthermore, western blotting revealed that the mechanism regarding the antiepileptic effect of may be related to the up-regulations of GAD 65 and GABAA in the brain. Collectively, we suggested that matrine can be developed as an effective antiseptic drug.
我们目前的研究旨在确定苦参碱的抗癫痫活性，并探索其可能的分子机制。为了评估苦参碱的抗癫痫活性，建立了由戊四氮（PTZ）和最大电休克（MES）诱导的小鼠癫痫模型，然后还进行了戊巴比妥钠诱导的小鼠麻醉时间和运动活性测试。对于分子机制研究，测定了癫痫小鼠中天门冬氨酸（Asp）、γ-氨基丁酸（GABA）、谷氨酸（Glu）、甘氨酸（Gly）的含量；然后，制备了由PTZ诱导的慢性癫痫大鼠，并使用蛋白质免疫印迹法测定大脑中谷氨酸脱羧酶65（GAD 65）、γ-氨基丁酸A型受体（GABAA）和γ-氨基丁酸B型受体（GABAB）的表达。结果显示，苦参碱对MES和PTZ诱导的癫痫小鼠具有显著的抗癫痫作用。此外，戊巴比妥钠诱导的麻醉时间和运动活性测试也表明苦参碱具有明显的抗癫痫作用。另外，我们的结果显示，用苦参碱治疗后，GABA的含量可以升高，而Glu的含量明显降低。此外，蛋白质免疫印迹法显示，苦参碱抗癫痫作用的机制可能与大脑中GAD 65和GABAA的上调有关。总的来说，我们认为苦参碱可以开发成为一种有效的抗癫痫药物。
