TrkB、P75^(NTR)在颞叶癫痫大鼠海马中的表达及托吡酯干预的研究  

EXPRESSIONOF TRKB AND P75^(NTR) IN HIPPOCAMPUS OF RAT MODEL OF TEMPORAL LOBE EPILEPSY AND THE EFFECT OF TOPIRAMATE

作　　者：余璐[1] 梁秀琳[2] 郑金瓯[1] 

机构地区：[1]广西医科大学第一附属医院神经内科,南宁530021 [2]江苏省盐城市第三人民医院神经内科

出　　处：《广西医科大学学报》2012年第5期664-668,共5页Journal of Guangxi Medical University

基　　金：广西科学基金资助项目(No.桂科自0640118);广西卫生厅自筹课题(No.桂卫Z2010363)

摘　　要：目的:研究托吡酯(TPM)干预红藻氨酸(KA)致大鼠颞叶癫痫(TLE)后海马组织学变化特征及脑源性神经营养因子(BDNF)受体TrkB、P75NTR蛋白在大鼠海马内的表达,探讨TrkB及P75NTR在TLE中的作用及TPM的抗痫机制。方法:KA诱导建立TLE模型,观察大鼠行为学改变;于1d,1,2,3,4周时间点,用免疫组化法观察各组大鼠TrkB、P75NTR蛋白在海马内表达的改变,Nissl染色观察海马神经元丢失的变化。结果:(1)TPM干预后KA致痫大鼠发作减少。(2)KA致痫后海马神经元丢失以门区和CA1区为主,4周达高峰;TPM干预后海马神经元损伤明显减少。(3)致痫后,TrkB的表达于1d至4周在齿状回门区、CA3区明显增高(P<0.01),持续4周,在CA1区仅1d时增高(P<0.01);P75NTR的表达在PoDG、CA1区、CA3区明显增高(P<0.01),并在PoDG和CA3区持续至2周(P<0.05);TPM干预后TrkB、P75NTR于上述各区在时间和空间上的表达均明显减少。结论:致痫后,海马内TrkB和P75NTR的持续较长时间表达增高通过其受体起作用,可能有助于癫痫异常兴奋性网络的形成。TPM干预对海马神经元损伤有明显的保护作用,其机制可能为通过下调海马内TrkB和P75NTR的表达,减少海马神经元损伤从而对癫痫发展起潜在的神经保护作用。Objective： To investigate the characteristics of the histological changes and the brain derived neurotrophic factor （BDNF） receptor TrkB and P75NTR expression in hippocampus of a temporal lobe epilepsy （TLE） rat model induced by kainic acid （KA） after topiramate （TPM） intervention; and explore the effect of TrkB and P75NTR in TLE and the antiepileptic mechanism of topiramate. Methods： Adult rats were made to be a model of TLE by KA inducing status epilepticus. Behavioral changes were observed. TrkB and P75NTR protein was studied by immunohistochemistry at time points of 1d, 1w, 2w, 3w and 4w. Hippocampal neuron loss was detected by Nissl＇s staining. Results： （1） epileptic seizures were decreased after TMP intervention. （2） After KA-induced SE, cell loss in CA1 pyramidal cells and hillar neurons was prominent, achieving peak in 4w. The impairment of hippocampal neurons lessened significantly after TMP intervention. （3） after KA-induced SE, TrkB expression was increased significantly on PoDG and CA3 regions（ P d0.01）in ld-4w and lasted for 4 weeks; but was increased only in ld on CA1 region （ P 〈0.01） ; P75NTR expression was increased on PoDG, CA1 and CA3 regions （ P 〈0.01） and lasted for 2 weeks on PoDG and CA3 regions （ P 〈0.05）. The expression of TrkB and P75NTR was increased significantly on all of mention above regions either the time or the space after TPM intervention. Conclusion： The expression increased and lasting long time in TrkB and P75NTR in hippocampus were acted through their receptors and perhaps contributed to the persistent structure and functional changes of the formation in epilepsy. TPM intervention can obviously lessen the level of the KA- induced seizure and have an obvious protection to hippocampal neuron injury. After KA-induced SE, TPM probably has a potential protective effect during seizures by down-regulating Trk and P75NTR expression and then decreasing hippocampal neuron injury.

关 键 词：颞叶癫痫 BDNF TRKB P75 NTR 托吡酯 

分 类 号：R742.1[医药卫生—神经病学与精神病学]