迷走神经电刺激抑制癫痫大鼠脑内多药耐药相关蛋白的过表达

Vagus nerve stimulation inhibiting multidrug resistance-associated protein 1 over-expression in drug refractory epilepsy rats

目的研究迷走神经电刺激fVNS）对药物难治性癫痫大鼠脑内多药耐药相关蛋白（MRPl）表达变化的影响。方法在颞叶癫痫（TLE）大鼠模型基础上，通过苯巴比妥钠（PBl的诱导，筛选出耐药大鼠。将耐药大鼠按照随机数字表法分为VNS组（7只）、假VN组（6只）和对照组（6只），VNS组连接刺激设备并进行VNS，假VNS组连接刺激设备但不进行刺激，对照组不连接刺激设备，常规饲养。实验全过程用视频脑电系统进行同步监控。比较3组大鼠行为学变化及痫性发作次数，同时比较迷走神经电刺激4周之后各组大鼠脑内MRP1的表达变化情况。结果（1）VNS组大鼠癫痫发作（2．6±1．0）次，假VNS组发作（5．3±1．1）次，对照组发作（5．2±1．3）次，VNS组较后2组发作次数显著减少，差异有统计学意义（P〈0．05）。（2）VNS组MRP1免疫组化染色结果吸光度值为9120±1496，假VNS组为19556±1462，对照组为20231±1710，VNS组较后2组显著降低，差异有统计学意义（P〈0．05）。结论VNS能够减少耐药癫痫大鼠的痫性发作次数，推测机制为降低大鼠脑内MRP1的表达量。

Objective To study the effect of vagus nerve stimulation （VNS） on the expression of multidrug resistance-associated protein （MRP1） in brains of rats with drug refractory epilepsy. Methods Rat models based on the lithium-pilocarpine epileptic rats were induced with sodium phenobarbital （PB）. Then, the rats were randomly divided into three groups： VNS group （n=7）, sham-VNS group （n=6） and control group （n=6）; VNS through stimulation device was given to the rats in the VNS group, stimulation device without VNS was given to the rats in the sham-VNS group, and rats in the control group were only given conventional feeding. Behavioral changes and number of seizures were recorded by continuous video monitoring during the whole process. And the amount of MRP1 over-expression in each group was detected following a four-week VNS. Results （1） The seizure frequency in VNS group （2.6±1.0 per week） was significantly decreased as compared with that in sham-VNS group （5.3±1.1 per week） or control group （5.2±1.3 per week） after a four-week VNS （P〈0.05）. （2） The MRP1 expression in VNS group had significantly statistical differences as compared with that in the sham-VNS group and control group （the absorbance values： 9120±1496, 19556±1462 and 20231±1710, P〈0.05）. Conclusion VNS can effectively decrease the seizures frequency through reducing the MRP1 over-expression.