目的 探讨在戊四氮(pentetrazole,PTZ)致癫痫大鼠海马组织中Homer1a、mGluR5的表达以及丙戊酸钠(sodium valproate,VPA)对其表达的影响。方法 将SD大鼠分为正常对照组(NC)、PTZ组和VPA干预组。PTZ腹腔注射达到点燃标准,腹腔注入VPA 15 mg/(kg·d),对致痫大鼠进行治疗;30 min后,腹腔注射PTZ诱发癫痫发作;两周后分别于致痫大鼠发作后8 h、24 h处死大鼠;应用实时定量PCR(realtime-PCR)、Western blot技术检测海马组织Homer1a、mGluR5的表达。结果 1)NC组无癫痫发作,VPA干预组癫痫发作较PTZ组减轻;2)PTZ组Hmoer1a于癫痫发作后8h明显升高,24 h后则明显降低;VPA干预组Homer1a表达于癫痫发作后8 h及24 h均升高;3)PTZ组mGluR5表达于癫痫发作后8 h无显著变化,而24h后明显升高;VPA干预组mGluR5表达于癫痫发作后8 h无显著变化,24 h后明显降低。 结论 1)丙戊酸钠可明显改善致痫大鼠发作表现;2)Homer1a 在癫痫发作后早期短暂性升高;mGluR5 在癫痫发作后早期无明显变化,而发作后24 h升高;3)丙戊酸钠可能通过调节Homer1a表达进一步影响mGluR5而发挥抗痫作用。
Abstract
Objective To study the effects of sodium valproate(VPA )on homer1a and mGluR5 expression in Hippocampal tissue of epileptic rats. Methods SD rats were divided into normal control(NC) group,pentetrazole (PTZ) group and VPA group.PTZ was intraperitoneally injected once every 48 h.Fully kindled rats of VPA group were injected with VPA[15mg/(kg·d)],while the rats of PTZ group were injected with normal saline.After 30 minutes,seizures were induced with the same dose of PTZ.Realtime-PCR was performed to examine the mRNA expression of Homer1a and mGluR5,Western-blot was used to detect the protein expression of them.Results 1)The rats of NC group had no seizure activity;those of VPA group showed slighter seizure activity than PTZ group.2)The expression level of Homer1a increased from 8 h after the last seizure,and decreased to the normal level 24 h later;the level of both them in VPA group increased in 8 h and 24 h after the last seizure.3)The level of mGluR5 in 8 h after the last seizure had no signifitant difference compared to NC group.mGluR5 expression was upregulated in 24 h after seizure and was downregulated in VPA group. 【Conclution】 1)VPA can alleviate the degree of seizure.2)Homer1a can increase transiently in early phase of epileptogenesis,mGluR5 can be upregulated in recovery phase.3)VPA may affect the expression of mGluR5 by regulating Homer1a for anti-epileptogenesis.
关键词
癫痫 /
丙戊酸钠 /
Homer1a /
mGluR5
Key words
epilepsy /
valproate /
Homer1a /
mGluR5
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基金
山东省自然科学基金(ZR2012HQ035);滨州市科技发展计划(2011ZC0905);滨州医学院科技发展计划(BY2009KJ18)
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