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不同成熟期大鼠戊四氮反复惊厥模型与癫痫发病机制研究 被引量:4

A rat model of repeated seizures induced by pentylenetetrazol at different maturational stages and the role of NF-κB in the pathogenesis of epilepsy
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摘要 目的:观察新生大鼠、成熟大鼠反复惊厥后海马结构的变化及NF-κB表达,探索未成熟脑癫痫发病机制。方法:对生后10d、60d(P10、P60)两实验组大鼠用戊四氮(PTZ)反复腹腔注射5d,设P10、P60生理盐水对照组;硫堇染色对CA1、CA3、DG及门区神经元进行细胞计数,观察海马神经元坏死及凋亡;免疫组化技术检测NF-κB的表达;Timm组织化学染色观察苔藓纤维发芽并评分。结果:(1)P10实验组与对照组比较,海马齿状回、CA1、CA3区无明显神经元丢失,DG区颗粒细胞数在实验组(23.25±3.06)多于对照组(16.25±1.58);P60实验组CA1、CA3区神经元计数(8.22±1.88、5.62±1.68)明显少于对照组(6.31±1.50、3.62±1.40),DG区无明显差异;(2)两实验组CA3区锥体层苔藓纤维发芽均多于对照组,但P60(3.25±1.03)较P10(1.50±0.92)更明显;(3)P10、P60实验组NF-κB表达高于对照组,且P10组较P60组更为明显(P<0.05)。结论:新生大鼠致痫后海马神经元无明显丢失,脑内NF-κB表达增加,可能是未成熟脑对惊厥性脑损伤具有耐受性的重要神经生物学基础。 AIM: To observe histopathologic changes and NF-κB expression in hippocampus in neonatal and matural rats after repeated seizures, and to explore the role of NF-κB in the pathogenesis of epilepsy in premature brain of rats. METHODS: Neonatal rats and mature rats were divided into 2 experimental groups at 10 days and 60 days after birth (P10 and P60). Convulsions were induced by repeated injection of pentylenetetrazol (PTZ) intraperitoneally for first 5 days. The animals in control group were injected with NS at the same volume in the same conditions. The neurons in CA1, CA3, dentate granule (DG), as well as in hilar were counted by thionin staining, in order to observe the profile of the necrosis and apoptosis. NF-κB expression was examined by immunohistochemistry assay. Timm's method of silver sulfide staining was adopted to observe the mossy fiber sprouting. RESULTS: (1) In immature rats (10 days old), neurons in CA1, CA3 and hilar demonstrated no differences from controls, whereas adult rats (P60) had a significant decrease in number of neurons in CA1 and CA3 (8.22±1.88, 5.62±1.68 vs 6.31±1.50, 3.62±1.40). In adult rats, neurons in dentate granule showed no differences with controls, whereas immature rats with daily seizures had a significant increase (23.25±3.06 vs 16.25±1.58). (2) There was prominent sprouting in the CA3 stratum pyramidal layer in all experimental rats after 5 daily seizures, regardless of the age. However, the degree of sprouting was significantly different between the two experimental groups (3.25±1.03 vs 1.50±0.92, P<0.05). (3) NF-κB was highly expressed in CA3, CA1 and DG after 24 hours by PTZ-kindling, whereas it was little expressed in control group. NF-κB expression was higher in P10 experimental rats than that in P60 rats. CONCLUSION: No cell loss was observed in hippocampus in neonatal rats after recurrent kindling. The high expression of NF-κB may be one of the important molecular mechanisms underlying the special resistance of the neurons in premature brain to the epileptic cerebral lesions.
作者 黄亚玲 孙丹
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2005年第7期1401-1405,共5页 Chinese Journal of Pathophysiology
基金 湖北省自然科学基金资助项目(No.2004ABA234)
关键词 海马 惊厥 戊四氮 NF-KB 大鼠 Hippocampus Seizure Pentylenetetrazol NF-κB Rats
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参考文献11

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