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目的观察巢蛋白(nestin)和骨形成蛋白4(BMP4)基因在戊四氮(PTZ)点燃癫大鼠海马中的表达,并探讨两者与癫发病机制的关系。方法将81只成年雄性SD大鼠随机分为实验组(n=54)和对照组(n=27)。实验组采用PTZ点燃癫大鼠,按点燃中的不同时相点,又随机分为9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,观察海马nestin和BMP4表达的变化。结果nestin阳性细胞在PTZ注射后3d开始出现在齿状回、CA3区和CA1区,到7d达到高峰,以后逐渐减少。BMP4在PTZ注射后7d开始增多,在点燃后1d达到高峰,以后逐渐减少,主要分布在齿状回、CA3区和CA1区。结论PTZ点燃可引起海马内星形胶质细胞增生、活化和神经发生,这可能是癫海马组织胶质化、神经元可塑性的病理基础;BMP4可能在PTZ癫形成过程中起重要作用。
Objective To investigate the expression of nestin and bone morphogenetic protein 4 (BMP4) gene in the hippocampus of pentylenetetrazole (PTZ) -induced epileptic rats and to explore their relationship with the pathogenesis of epilepsy. Methods Eighty-one adult male Sprague-Dawley rats were randomly divided into experimental group (n = 54) and control group (n = 27). In the experimental group, PTZ was used to ignite the epileptic rats, which were randomly divided into 9 groups at different time points of ignition. The expression of nestin and BMP4 in hippocampus was observed by immunohistochemistry and digoxigenin-specific oligonucleotide probe in situ hybridization histochemistry. Results Nestin positive cells began to appear in the dentate gyrus, CA3 and CA1 areas 3d days after PTZ injection, reaching the peak at 7d and then decreasing gradually. BMP4 began to increase at 7d after injection of PTZ and peaked at 1d after ignition, then gradually decreased, mainly distributed in dentate gyrus, CA3 area and CA1 area. Conclusion PTZ can cause astrocyte proliferation, activation and neurogenesis in the hippocampus, which may be the pathological basis of glialization and neuronal plasticity in hippocampal formation of hippocampus. BMP4 may play an important role in PTZ epilepsy formation.