熄风胶囊对匹罗卡品致痫大鼠电压门控性钠通道功能的影响

Research of the effect of Xifeng Capsule on the function of voltage-gated sodium channel in epileptic rats induced by pilocarpine

关键词:  电压门控性钠通道  熄风胶囊  癫痫  全细胞膜片钳

Key words:  Voltage-gated sodium channel  Xifeng Capsule  epilepsy  whole cell patch clamp

摘要:

[目的]研究中药复方熄风胶囊对氯化锂-匹罗卡品致痫大鼠海马神经细胞电压门控性钠通道（VGSC）功能的影响。[方法]建立氯化锂-匹罗卡品致痫大鼠模型。将实验大鼠随机分为空白组、模型组、熄风胶囊低剂量治疗组（熄低组）、熄风胶囊中剂量治疗组（熄中组）和熄风胶囊高剂量治疗组（熄高组）。通过全细胞膜片钳检测海马神经细胞VGSC功能的变化。[结果]1）成功复制氯化锂-匹罗卡品大鼠模型。与模型组比较，熄高组、熄中组和熄低组发作次数均低于模型组（P<0.01），而熄风胶囊治疗组中，随剂量增加发作次数逐渐减少，其中熄高组和熄低组比较差异有统计学意义（P<0.05）。2）全细胞膜片钳记录钠电流结果：与空白组比较，各组的钠电流密度明显增加、激活曲线阈值下降、失活曲线阈值上升、失活后恢复时间缩短，差异有统计学意义（P<0.01）；与模型组相比较，各熄风胶囊治疗组的钠电流密度下降、激活曲线阈值上升、失活曲线阈值下降、失活后恢复时间延长，差异有统计学意义（P<0.01）；各治疗组间比较，从电流-电压曲线可见，熄高组和熄中组相比有随剂量增加而电流下降趋势，但无统计学意义（P>0.05），而熄高组、熄中组分别与熄低组比较有显著性差异（P<0.01）；激活曲线和失活可见各中药治疗组之间，随剂量升高电流有下降趋势，提示治疗后激活和失活阈值有上升趋势，但各治疗组间无统计学意义（P>0.05）；失活后恢复曲线可见总体上随剂量升高恢复时间有延长趋势，但各治疗组间无统计学意义（P>0.05）。[结论]熄风胶囊通过减少VGSC电流，增强VGSC失活，抑制失活后的恢复，延长恢复时间来达到降低VGSC异常活化的作用，从而降低癫痫反复自发性发作，这可能是其作用机制之一。

Abstract:

[Objective] To study he effect of Xifeng Capsule on the function of voltage-gated sodium channel in hippocampus of epileptic rats induced by lithium chloride and pilocarpine.[Methods] The epileptic rat model was induced by lithium chloride and pilocarpine. The experimental rats were randomly divided into 5 groups:blank group,model dose group,low dose group of low dose group of Xifeng Capsules (low dose group),medium dose group of Xifeng Capsules (medium dose group),and high dose group of Xifeng Capsules (high dose group). VGSC function of hippocampal nerve cell was detected through the whole cell patch clamp techniques.[Results] 1)lite-pirocarpine rat model was duplicated successfully. Compared with model dose group,the number of episode times of high dose group,extinguish the episodes and low dose group were less than model dose group (P<0.01). With the increase of the dose,the number of episode times reduced gradually,and there was statistically significance in the number of episode times between high dose group and low dose group (P<0.05). 2)Total cell patch clamp to record sodium current results:compared with the blank group,the sodium current density of each group significantly was increased,the threshold value of activation curve was decreased,the threshold value of inactivation curve was increased,and the recovery time after inactivation was shortened,and there were statistically significance in all these results (P<0.01). Compared with the model group,the sodium current density of all Xifeng Capsule groups were decreased,activation curve threshold were increased,inactivation curve threshold were decreased,and recovery time were prolonged,and there were statistically significance in all these results (P<0.01). Compared with the medium dose group,the current of the high dose group tended to decrease,but there was no statistical significance in two groups (P>0.05),while compared with the low dose group,the current of the medium dose group and the high dose group showed significant difference (P<0.01). As to the activation curve and inactivation in all dose groups,with the increase of the dose,the value of activation and inactivation tended to decrease,but there was no statistical significance between the treatment groups (P>0.05). The recovery curve of inactivation showed an overall extension tendency with the increase of dose recovery time,but there was no statistical significance between the treatment groups (P>0.05).[Conclusion] Xifeng Capsule may reduce the abnormal activation of sodium channel by reducing sodium channel current,increasing the inactivation of sodium channel,inhibiting the recovery after inactivation,and prolonging the recovery time,thus reducing recurrent spontaneous seizures,which may be one of its mechanisms.