左乙拉西坦对致痫大鼠海马组织中BMP4表达的影响

目的：建立氯化锂－匹罗卡品幼年大鼠癫痫模型，观察左乙拉西坦对癫痫海马组织中骨形成蛋白（BMP4）表达的影响，以探讨左乙拉西坦的抗癫痫作用机制。方法：将116只21d龄Wistar雄性大鼠随机分为4组，其中空白对照组（NS组）24只、左乙拉西坦对照组（LEV对照组）24只、氯化锂一匹罗卡品模型组（PILO组）34只、氧化锂一匹罗卡品模型＋左乙拉西坦治疗组（LEV治疗组）34只。PILO组和LEV治疗组大鼠首先给予腹腔注射氯化锂（125mg／kg）进行诱导，16h后腹腔注射硫酸阿托品（1mg／kg），30min后再以匹罗卡品（60mg／kg）腹腔注射，如果没有癫痫发作，可在半小时后，再次腹腔注射匹罗卡品15rag／kg，直至充分点燃建立癫痫模型。其中，LEV治疗组，每日给予左乙拉西坦200mg／kg，连续3周进行灌胃治疗，并分别于1周，2周，3周，处死各组大鼠，并通RT--PCR的方法分别检测及观察海马组织中BMP4表达的变化。结果：PILO组与NS对照组相比，BMP4的表达增加，第1周达高峰（P〈0．01），第2周、第3周BMP4表达逐渐下降，但较NS对照组仍高表达（P〈0．05），LEV治疗组与PILO对照组相比，BMP4表达逐渐降低（P〈0．05），LEV对照组与NS对照组无统计学意义（P〉0．05）。结论：癫痫发作后BMP4表达增加，提示BMP4与癫痫形成密切相关，左乙拉西坦可能通过抑制海马组织中BMP4表达而发挥抗癫痫发作。

Effect of l evetiracetam on expression of BMP4 in hippocampus of epilepsy rats

Objective： To establish the lithium pilocarpinemodel of epilepsy in young rats, and observe the effect of levetiraeetam on forming protein in hippoeampus of epilepsy of bone （BMP4） so as to explore the mechanism of antiepileptic effect of levetiracetam. Methods： 116 Wistar male rats 21 day old were randomly divided into four groups, including blank control group （group NS） 24, levetiracetam group （LEV group） 24, lithium chloride pilocarpine model group （PILO group） 34, lithium chloride pilocarpine model ＋ left B La Tan treatment group （LEV group） 34. PILO group and LEV group rats were first given intraperitoneal injection of lithium chloride （125mg/kg）, after 16h hours intraperitoneal injection of atropine sulfate （lmg/kg）, after 30 minutes the intrpritoneal injection of pilocarpine （60mg/kg）. If there is no seizures, intraperitoneal injection of piloearpine 15mg/kg was given after half an hour until fully kindling epilepsy model. Among them, LEV treatment group were given daily doses of levetiracetam 200mg/kg, for three consecutive weeks of garage treat- ment. At 1 week, 2 weeks, 3 weeks, all the rats were sacrificed, and through RT--PCR to detect and observe the expression changes of BMP4 in hippocarnpus. Results： Compared with PILO group and NS control group, BMP4 expression increased and reached the peak at first week （P ~ 0. 01）, the expression of BMP4 at second weeks and third weeks were gradually decreased, but it was still high compared with the NS group （P 〈 0.05）. Compared to the LEV treatment group and PILO control group, the expression of BMP4 decreased gradually （P 〈 0.05 no statistical significance）. There was no statistic significance of LEV control group and NS control group （P 〉 0. 05）. Conclusion： After the incidence of seizures, BMP4 expression increased, which suggested that BMP4 and epilepsy is closely related to the formation. Levetiracetam may play its role by inhibiting the expression of BMP4 in hippocampus exert anti epileptic seizures.