全天麻及天麻素联合卡马西平对癫痫小鼠脑部海马体神经元及基因mrp1表达的影响

Effects of gastrodia capsule and gastrodin combined with carbamazepine on the hippocampal neurons and the expression level of mrp1 gene of PTZ-kindled mice

目的:本研究旨在说明全天麻胶囊及天麻素联合卡马西平应用于抗癫痫治疗后,对于卡马西平抗癫痫作用的影响及作用机制。方法:通过戊四唑诱导的癫痫小鼠模型,采用癫痫模型发作等级评分,对不同给药组癫痫模型小鼠进行评分,以判断联合给药后卡马西平抗癫痫作用。通过普通病理学、RT-PCR研究全天麻胶囊及天麻素联合卡马西平对癫痫小鼠脑部海马体神经元及多药耐药相关蛋白基因(mrp1)的影响。结果:全天麻及天麻素联合卡马西平能够显著提高卡马西平的抗癫痫作用,全天麻胶囊可改善海马CA3区神经元损伤,而天麻素及卡马西平则无该类作用。全天麻胶囊可逆转因多次给药引起的mrp1基因的高表达,天麻素则会在多次给药后诱导mrp1基因高表达。结论:全天麻胶囊可提高卡马西平的抗癫痫小鼠作用,与减轻海马神经元损伤及降低mrp1基因高表达相关。

Objective： This study was designed to illustrate the antiepileptic effects and possible mechanisms of gastrodia capsule and gastrodin combined with carbamazepine on PTZ-kindled mice,and further revealed the influence of gastrodia capsule and gastrodin on the antiepileptic action of carbamazepine. Methods：The states of epileptic seizure of amyl tetrazolium（ PTZ）-induced epileptic mice were scored,to measure the antiepileptic effect of gastrodia capsule and gastrodin combined with carbamazepine. Then the general pathology and RT-PCR methods were used to study the effects of gastrodia capsule and gastrodin combined with carbamazepine on the hippocampus nerve cells and the expression level of mrp1. Results： The gastrodia capsule and gastrodin can significantly increase the antiepileptic effect of carbamazepine. The gastrodia capsule can significantly attenuate the damage of hippocampus CA3 pyramidal neurons, but gastrodin cannot. Further, the gastrodia capsule can dramatically revert the high expression level of mrp1 after multiple dosage of carbamazepine,on the contrary,the gastrodin cannot,and even further increase the expression level of mrp1 after multiple dosage of carbamazepine.Conclusion： The gastrodia capsule can significantly increase the antiepileptic effect of carbamazepine,and can also attenuate the damage of hippocampus CA3 pyramidal neurons and decrease the high expression level of mrp1 aftermultiple dosage of carbamazepine. Nonetheless,the underlying mechanism for antiepileptic activity of gastrodia capsule still needs further study.