目的 研究桃红四物汤的抗癫痫作用机制。方法 建立戊四氮（PTZ）点燃大鼠癫痫模型，随机分为对照组、模型组和桃红四物汤低、中、高剂量组。桃红四物汤剂量分别为0.7、1.4、2.1 g/kg，给药体积为10 mL/kg，每日ig给药1次，连续给药2周。给药第0、14天观察大鼠癫痫发作程度。给药结束处死大鼠，伊文思蓝（EB）法测定血脑屏障通透性，Western blotting法和免疫荧光法测定脑组织及不同部位3种紧密连接蛋白：闭锁连接蛋白-1（ZO-1）、基质金属蛋白酶-9（MMP-9）、Occludin蛋白表达水平。结果 高、中、低剂量桃红四物汤可显著降低大鼠癫痫发作程度和血脑屏障通透性（P< 0.01）。低剂量桃红四物汤可显著升高大鼠脑组织皮层、海马及纹状体的MMP-9表达水平（P< 0.05）；中、高剂量桃红四物汤可显著升高大鼠脑组织ZO-1、MMP-9、Occludin表达水平（P< 0.05、0.01）。结论 桃红四物汤可显著减轻癫痫发作程度，作用机制可能与降低血脑屏障通透性及升高脑组织紧密连接蛋白表达水平有关。

Objective To investigate the anti-epileptic mechanism of Taohong Siwu Decoction (TSD) on the seizures degree and blood-brain-barrier (BBB) of epileptic animals. Methods A rat model of epilepsy was induced by pentamethylene. Rats were randomly divided into normal group, model group, and TSD groups. Rats in TD groups were respectively ig given 0.7, 1.4, and 2.1 g/kg TSD, once daily for successive 2 weeks. Epileptic seizures degree was observed on day 0 and 14. BBB permeability was evaluated by Evans blue method on day 14. Expression levels of zona occulden-1 (ZO-1), matrix metalloproteinase-9 (MMP-9), and Occludin in brain and different parts of brain were determined by Western blotting and immunofluorescence methods. Results All doses of TSD significantly reduced rats' epileptic seizures degree and BBB permeability (P < 0.01). TSD at a dose of 0.7 g/kg can significantly increase the expression of MMP-9 in cortex, hippocampus, and striatum of rats (P < 0.05). TSD at doses of 1.4 and 2.1 g/kg could significantly increase the expression of ZO-1, MMP-9, and Occludin in brain tissue of rats (P < 0.05, 0.01). Conclusion TSD can significantly reduce epileptic seizures degree, which may be related to its BBB protective effects and its potent to increased tightly bind protein in brain.

山东省自然科学基金项目（Y2008C1610）