辛伐他汀抑制慢性颞叶癫痫形成的初步研究

Effect of simvastatin on chronic temporal epilepsy in rats

目的研究辛伐他汀对慢性颞叶癫痫大鼠脑组织病理改变及癫痫发作的影响。方法成年雄性Wistar大鼠72只按照随机数字表法分为对照组、盐水组及辛伐他汀组，每组24只。对照组大鼠单侧脑室内单次注入生理盐水1μL；盐水组大鼠单侧脑室内注入海人酸（KA）致痫成功0．5h后，生理盐水灌胃（1nag每公斤体质量），每日1次，连续14d；辛伐他丁组大鼠单侧脑室注入KA致痫成功0．5h后，进行辛伐他汀灌胃（1mg每公斤体质量），每日1次，连续14d。致痫后3d、4个月、5个月、6个月4个时间点处死大鼠，制作脑组织石蜡切片进行Timm’s染色、Nissl染色、GFAP染色，观察慢性颞叶癫痫大鼠脑组织病理改变；同时记录大鼠的癫痫发作，参照Racince’s分级法分级并计分。结果与盐水组相比，辛伐他丁组小鼠CA3区和齿状回的神经元丢失减少，胶质细胞增生减少，苔状纤维发芽程度明显减轻，癫痫发作级别降低，差异有统计学意义（P＜0．05）。结论辛伐他汀在慢性颞叶癫痫的形成过程中起到了长期的神经保护作用。

Objective To examine the effect of administration of simvastatin on pathological changes of brain tissues from rats with chronic temporal lobe epilepsy （TLE） and epileptic seizure of these rats. Methods Seventy-two adult male healthy Wistar rats were randomly divided into control group, saline treatment group and Simvastatin （Sire） treatment group （n=24）. Rats of the control group were only received oral administration of saline into unilateral ventricle; status epilepticus （SE） in rats of saline treatment group and Sim treatment group were induced by kanic acid （KA） injection into unilateral ventricle; 0.5 h after SE, rats of the saline treatment group were treated with oral administration of saline once daily for 14 consecutive days; rats of the Sim treatment group were subjected to oral administration of simvastatin once daily for 14 consecutive days. Rats were sacrificed 3 d, 4, 5 and 6 months after simvastatin or saline administration. Timm＇s staining, Nissl staining, and GFAP staining were employed to observe the pathological changes of these rat brain tissues; and the seizures were observed and scored according to Racine＇s grading. Results Pathological changes showed that loss of neurons in the CA3 and the dentate gyrus was obviously restrained, speed of mossy fiber sprouting was significantly slowed down, and the grade of SE was significantly decreased in rats of the Sim treatment group as compared with those in rats of saline treatment group （P〈0.05）. Conclusion Simvastatin may have long-term neuroprotective effect on process of chronic TLE.