【摘要】 目的探讨左乙拉西坦干预对癫痫大鼠痫性发作及海马缝隙连接蛋白43(Cx43)表达的影响。方法健康成年SD雄性大鼠32只,随机分为癫痫组、左乙拉西坦干预组(左乙拉西坦组)、甘珀酸干预组(甘珀酸组)和正常对照组,每组8只。用氯化锂-匹罗卡品注射制作癫痫大鼠模型,甘珀酸组大鼠在注射匹罗卡品前30 min,腹腔注射甘珀酸20 mg/kg;左乙拉西坦组大鼠在注射匹罗卡品前60 min,予左乙拉西坦300 mg/kg灌胃;癫痫组大鼠不干预。观察各组大鼠的癫痫发作潜伏期,以及制模后2 h、12 h、24 h的发作(Racine分级≥3级)次数,并持续脑电监测。采用Western-blot法和RT-PCR法检测大鼠海马组织Cx43的表达。结果左乙拉西坦组和甘珀酸组的癫痫发作潜伏期明显长于及发作次数明显少于癫痫组(P<0.05～0.01);左乙拉西坦组的痫性发作次数又明显少于甘珀酸组(P<0.05)。甘珀酸和左乙拉西坦组大鼠的脑电图为散在低幅尖波,明显比癫痫组的(持续高幅棘波、棘-慢波综合)轻。各癫痫模型组的海马Cx43表达水平均明显高于正常对照组(均P<0.05),而左乙拉西坦组和甘珀酸组的海马Cx43表达水平明显低于癫痫组(均P<0.05),两干预组海马Cx43表达水平的差异无统计学意义。结论左乙拉西坦干预对癫痫大鼠的痫性发作有显著效果;并能明显抑制大鼠海马Cx43的表达;这可能是其治疗癫痫的作用机制之一。更多还原

【Abstract】 Objective To explore the effect of levetiracetam( LEV) interention on the seizures and expressions of connexin 43( Cx43) of hippocampus in epileptic rats. Methods Thirty-two SD rats were randomly divided into epileptic model group,LEV interention group( LEV group),carbenoxolone interention group( carbenoxolone group) and normal control( NC) group,8 rats in each group. Epileptic rat models were made by lithium chloride-pilocarpine method. The rates in carbenoxolone group were given 20 mg / kg carbenoxolone by introperitoneal injection 30 minutes before pilocarpine injected,and the rates in LEV group were given LEV 300 mg / kg by intragastric administration 60 minutes before pilocarpine injected,while epileptic model group were no intervention. The latency of seizures and the times of seizures( above Racine Ⅲ level) in 2 h,12 h and 24 h after models made were observed. And EEG was continuously monitoring. The expressions of connexin 43 of hippocampus areas in rats were detected with Western-blot and RT-PCR. Results The latency and times of seizures in LEV group and carbenoxolone group was significantly longer and less than those in the epileptic model group( P < 0. 05- 0. 01). While the times of seizures in LEV group were significantly less than that in carbenoxolone group( P < 0. 05). The EEG in carbenoxolone group and LEV group was scattered low-amplitude sharp waves,and better than that in epileptic model group( sustained high-spike waves and spike-slow waves complex). The expression levels of connexin 43 of hippocampus in all epileptic models made groups were significantly higher than that in the NC group( all P < 0. 05). While the expression levels of connexin 43 of hippocampus in LEV group and carbenoxolone group were significantly lower than that in epileptic model group( all P < 0. 05). There was no statistical significance on difference of expression levels of connexin 43 of hippocampus between two intervention groups. Conclusions LEV intervention has significant effects on seizures in epileptic rats, and can suppress obviously on the expressions of connexin 43 of hippocampus. This may be the mechanism of it antiepilepsy.更多还原