胡椒碱抗实验性癫痫作用及其作用机制分析

目的　研究胡椒碱的抗惊厥作用和作用机制。方法以不同的物理和化学方法引起小鼠和大鼠不同类型的惊厥 ,形成不同类型的实验性动物癫痫模型 ,预先ip不同剂量的胡椒碱 ,观察其有无抗惊厥作用。利用荧光分光光度计和氨基酸自动分析仪 ,分别测量小鼠脑内单胺类神经递质和氨基酸含量和大鼠脑片3H Glu释放实验分析其作用机制。结果　胡椒碱对多种实验性癫痫动物模型均有不同程度的对抗作用 ;对癫痫大发作动物模型MES、小发作动物模型Met和小鼠脑室注射 (icv)KA形成的颞叶性癫痫模型对抗作用较强 ,但对士的宁引起的强直性惊厥、3 巯基丙酸、荷包牡丹碱和兴奋性氨基酸引起的阵挛性惊厥均无明显的对抗作用。胡椒碱可明显增加小鼠脑内单胺类神经递质 5 HT的含量和明显降低Glu和Asp含量 ,并能降低 (Glu +Asp) /GABA的比值。 1× 10 -6 mol·L-1的胡椒碱对大鼠大脑皮层脑片预载的3H Glu的释放有明显的抑制作用。结论　胡椒碱有较强的抗惊厥作用。是一种广谱抗惊厥药。其机制可能与其增加动物脑内 5 HT和降低Glu及Asp的含量和阻断KA 受体有关

Analysis on the anti-experimental epilepsy action of piperine and its mechanism

AIM To study the anticonvulsive action of piperine on several experimental epilepsy models and analysis the mechanism of this action. METHODS Used different physical and chemical methods to induce different kinds of seizures in mice and rats, to make different kinds of experimental animal models of epilepsy, ip injection different doses of piperine in advance, to observe whether it has anticonvulsive effect or not. The concentrations of monoamine neurotransmitters and amino acids in mouse bran were determined by fluorescent spectrometer and amino acid auto analytic instrument respectively. RESULTS Piperine has different degree of anticonvulsive effects in different experimental animal models of epilepsy. The anticonvulsive effect is stronger in MES. Met and icv KA experiments, But no distinct effects on the tonic convulsion induced by strychnine and clonic seizures induced by 3 Mp?Bic?glutamate?and NMDA. Piperine was found to be able to increase the concentrations of 5 HT and 5 HIAA,decrease the concentrations of glutamate?aspartate and the ratio (Glu+Asp)/GABA. Piperine at the concentration of 1×10 -6 mol·L -1 can obviously decrease the release of 3H glutamate from rate brain cortex slice. CONCLUSION Piperine has stronger anticonvulsive action. The mechanism of such action may be related to increase the concentration of 5 HT and decrease glutamate, aspartate and block the KA R in the mouse brain.