PTZ点燃癫痫大鼠海马NSE和BMP4的表达

Experimental study of neuron specific enolase and BMP4 expression in hippocampus of pentylenetetrazol kindled epilepsy rats

目的观察神经元特异性烯醇酶(neuron-specific enolase,NSE)和骨形成蛋白4(bone morphogenic protein4,BMP4)基因在戊四氮(pentylenetetrazol,PTZ)点燃癫痫大鼠海马中的表达,并探讨两者与癫痫发病机制和脑损伤的关系。方法将50只成年雄性SD大鼠分为对照组和实验组。实验组采用PTZ点燃癫痫大鼠,按点燃进程,又随机分为Ⅰ级组、Ⅲ级组、Ⅳ级组和Ⅴ级组。用免疫组化技术、地高辛标记特异性寡核苷酸探针原位杂交组织化学技术和图像分析技术,观察海马NSE和BMP4表达的变化。结果发现应用PTZ点燃后,随发作级别的增高,大鼠海马各区NSE和BMP4的表达亦增加。在Ⅲ和Ⅳ级大鼠海马CA3及DG的NSE和BMP4表达明显高于对照组(P<0·01);Ⅴ级大鼠在发作后海马CA3及DG的NSE和BMP4表达呈逐渐下降。结论PTZ点燃可诱导癫痫海马内神经元损伤和神经发生增加,这可能是癫痫海马内神经元丢失、神经元可塑性的病理基础;NSE其表达水平与神经元损伤程度和预后密切相关;BMP4可能在PTZ癫痫形成过程中起重要作用。

Objective To investigate the expression of neuron-specific enolase （NSE） and bone genic protein 4 （ BMP4 ） explore their relationship in different hippocampal areas of pentylenetetrazol （PTZ） kindled epilepsy morphorats and with the pathogenesis of epilepsy and brain injury. Methods Fifty male SD rats were divided into experimental group （n =40） and control group （n = 10）. The rats in experimental group were kindled into epilepsy by chemical method, and according to the kindling process, subdivided into four groups （grade Ⅰ , Ⅲ, Ⅳ, Ⅴ）. Immunohistochemistry, in situ hybridization labeled with Dig-oligonucleotide probe and the image analyzing system were used to observe the expressions of NSE and BMP4 in rat hippocampus. Results In PTZ kindled epilepsy rats, the number of cells positive for NSE and BMP4 was increased in many regions of hippocampal formation. Compared with control group, the expressions of NSE and BMP4 in CA3 and DG was elevated obviously in the grade Ⅲ group and grade Ⅳ group （ P 〈 0. 01 ） , but in the grade V group, the expressions of NSE and BMP4 in CA3 and DG was decreased gradually. Conclusion PTZ kindling can induce the neuron injury and increase neurogenesis, furter implying the pathologic base of neuron deletion and plasticity variation. The expression level of NSE was closely related with the degree of neuron damage and prognosis. BMP4 may play a critical role in the pathogenesis of PTZ kindling epilepsy.