丙戊酸镁干预对癫痫幼鼠海马区B1及B2激肽受体表达的影响

The effects of magnesium valproate on expression of the kinin B1 and B2 receptors in the hippocampus of the juvenile rats submitted to pilocarpine model of epilepsy

目的观察丙戊酸镁对氯化锂一匹罗卡品癫痫幼鼠模型海马区B1及B2激肽受体表达的影响并探讨其作用机理。方法健康幼鼠35只，采用氯化锂一匹罗卡品腹腔注射法制作癫痫模型，癫痫模型干预组15只，分为急性期丙戊酸镁干预组（12h，I组）、静止期丙戊酸镁干预组（5d，II组）、慢性期丙戊酸镁干预组（60d，Ⅲ组），每组5只；癫痫模型无干预组15只，分为急性期无干预组（6h，Ia组），静止期无干预组（5d，IIa组），慢性期无干预组（60d，Ⅲa组），每组5只；设置空白对照组5只（Ⅳ组）。丙戊酸镁均经鼻饲管给药，在干预后的相应时间点处死动物取海马标本，应用逆转录聚合酶链反应（RT．PCR）及westernblot方法分别检测各组动物不同时间点海马区的B1及B2激肽受体的表达变化，并相互进行此较。结果给予丙戊酸镁干预后，与Ia组（0．76±0．068、0．89±0．034；0．28±0．034、0．32±0．039）比较，I组B1激肽受体mRNA（0．38±0．051）及蛋白质表达（0．58±0．057）均显著下调，差异有统计学意义（P〈0．05），I组B2激肽受体mRNA（0．48±0．056）及蛋白质表达（0．48±0．044）均显著上调，差异有统计学意义（P〈0．05）；与IIa组（0．58±0．059、0．69±0．046；0．47±0．046、0．58±0．052）比较，Ⅱ组B1激肽受体mRNA（0．23±0．044）及蛋白质表达（0．394-0．034）显著下调，差异有统计学意义（P〈0．05），B2激肽受体mRNA（0．69±0．063）及蛋白质表达（0．794-0．063）显著上调，差异有统计学意义（P〈0．05）；与Ⅲa组（0．70±0．052、0．80±0．048）比较，Ⅲ组B2激肽受体mRNA（0．89±0．031）及蛋白质表达（0．91±0．031）显著上调，差异有统计学意义（P〈0．05）；与对照组比较，B1及B2激肽受体蛋白质表达Ia组、IIa组均显著增高，差异有统计学意义（P〈0．05），Ⅲa组B2激肽蛋白质表达（0．80±0．048）亦显著上调，差异有统计学意义（P〈0．05）。结论丙戊酸镁能降低海马区B1激肽受体表达，上调B2激肽受体表达，其保护机制与B激肽受体表达有关。

Objective To investigate the mechanisms and the effects of magnesium Valproate on the ex- pressions of the kinin B1 and B2 receptors in the hippocampus of the juvenile rats submitted to pilocarpine model of epilepsy. Methods 35 healthy Wistar juvenile rats were randomly divided into six groups, that is the model groups ： I group, Ⅱgroup, i group, and intraperitoneal injection of saline water control groups ： I a group, Ⅱ a group, llIa group , after succession of 15 rats to kindle to establish the model of epilepsy by pilocarpine. To collect hippocampus tissue after the rats were to put to death, and to compared the expression levels of kinin B1 and B2 receptor mRNA by RT-PCR and western blot in the hippoeampus of rats. Results By treated with magnesium val- proate, kinin B1 receptor mRNA （0.38 ±0. 051 ）and protein expressions（0.58 ±0. 057 ）decreased and kinin B2 reeeptor mRNA （0.48± 0.056 ） and protein expressions （0.48 ±0. 044 ） increased in [ group, compared with that （0.76±0.068,0.89±0.034;0.28 ±0.034,0.32±0.039） of I agroup（P〈0.05）. Compared with control group, there were more signifieant upregulation of kinin B1 receptor mRNA and protein expressions （P 〈 0.05 ） in the I and the Ⅱ groups and there were no alteration in Ill group. The expressional levels of B2 receptor mRNA and protein were upregulated in the Ⅰ , Ⅱ andⅢ groups. Conclusion The kinin B1 and B2 receptor may play a role in the onset and maintenance of epilepsy. The magnesium valproate increased the expressional levels of kinin B2 reeeptor,and decreased the expressional levels of kinin B1 receptor.