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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 morphogenic protein 4 (BMP4) genes in the hippocampus of pentylenetetrazol (PTZ) -induced epilepsy rats The relationship between them and the pathogenesis of epilepsy and brain injury. Methods 50 adult male SD rats were divided into control group and experimental group. Experimental group using PTZ ignition epileptic rats, according to the ignition process, and were randomly divided into Ⅰ group, Ⅲ group, Ⅳ group and Ⅴ group. The changes of NSE and BMP4 expression in hippocampus were observed by immunohistochemistry, digoxigenin-labeled oligonucleotide probe in situ hybridization histochemistry and image analysis. The results showed that after PTZ ignition, the levels of NSE and BMP4 in hippocampus of rats increased with the increase of seizures. The expressions of NSE and BMP4 in hippocampal CA3 and DG of rats in grade Ⅲ and grade Ⅳ were significantly higher than those in control group (P <0.01). The expression of NSE and BMP4 in hippocampal CA3 and DG decreased gradually in rats of grade Ⅴ. Conclusions PTZ can induce neuronal damage and increase of neuron in hippocampus, which may be the pathological basis of neuron loss and neuronal plasticity in epileptic hippocampus. The expression level of NSE is closely related to the degree of neuron injury and prognosis. PTZ play an important role in the process of epilepsy formation.