摘要
目的观察尼莫地平对血管性痴呆大鼠海马cAMP反应元件结合蛋白（CREB）和CCAAT增强子结合蛋白（C／EBP）的DNA结合活性的影响，探讨其治疗血管性痴呆的机制。方法66只sD大鼠随机分为模型组，假手术组和尼莫地平组，每组22只，采用4血管法制备大鼠血管性痴呆模型，分别给予生理盐水（8ml·kg-1·d-1）、尼莫地平（20mg·kg-1·d-1）灌胃，用HE染色法观察海马CA1区神经元形态变化，水迷宫法检测大鼠学习和记忆能力，凝胶电泳迁移率改变分析法（EMSA）测定海马组织CREB和C／EBP的DNA结合活性。结果水迷宫检测：尼莫地平组大鼠学习记忆能力[逃逸潜伏期（26．63±1．31）S，跨越平台次数（7．25±0．92）次]较模型组[逃逸潜伏期（41．25±1．83）S，跨越平台次数（5．33±0．64））次]强，差异有统计学意义（P〈0．05）。HE染色：模型组大鼠海马CAi区部分神经元正常结构消失，胞核区域浓染，出现凝固性坏死及细胞脱失，尼莫地平组大鼠海马CA1区神经元排列较模型组病理改变减轻，细胞结构完整；尼莫地平组海马CA1区正常神经细胞数目（43．19±2．87）较模型组（16．33±1．09）增加，差异有统计学意义（P〈0．05）。EMSA：尼莫地平组CREB和C／EBP的DNA结合活性[分别为（369．75±13．22），（428．25±17．69）]较模型组[分别为（142．25±27．86），（97．00±5．88）]均升高，差异有统计学意义（P〈0．01）。结论尼莫地平改善血管性痴呆大鼠海马神经元损伤和学习功能下降，可能与提高CREB和C／EBP的DNA结合活性有关。
Objective To observe the effect of nimodipine on hippocampal DNA-binding activity change of cAMP response element binding protein （ CREB ） and CCAAT enhancer binding protein （C/EBP） in a rat model of vascular dementia （VD） , and to explore the treatment mechanism of nimodipine. Methods 66 healthy adult male SD rats were assigned to the following three groups of 22 each ： VD model group, Sham-operated group, Nimodipine group. VD rat model was prepared by four-vessel occlusion. Physiological saline solution（ 8 ml·kg· d-1） and Nimodipine （20 mg-1·kg·d-1） were administered by gavage respectively. The Morris maze was adopted to detect the changes of spatial learning and memorizing capacity ,while HE straining was adopted to observe the changes of pathological characteristics in hippoeampal CA1 area,and electrophoretic mobility shift assay（EMSA） were adopted to observe DNA-binding activity changes of CREB and C/EBP in hippoeampus tissue. Results The Morris maze showed ：the learning and memory ability of nimodipine group rats（ escape latency period （26.63 ± 1.31 ） s, the times of cross-platform（7.25 ± 0.92 ） times） was higher than that of VD model group （ escape latency period （41.25 ± 1.83 ） s, the times of cross-platform （ 5.33 ± 0.64 ） times）, with difference of statistical significance （P 〈 0.05 ） . HE results ： in VD model group, neurons in CA1 were scattered and boundaries were unclear, nuclei region was stained, coagulation necrosis appeared, obviously cells lost. The CA1 neurons of nimodipine group returned to be normal, nuclear membrane＇s profile and nudeolus were clear, regularly arranged; the number of hippocampal normal neurons in nimodipine group （43.19 ±2.87） was more than that of VD model group（ 16.33 ± 1.09） ,with difference of statistical sigalificance（P 〈 0.05）. EMSA：both CREB and C/EBP DNA-binding activity in rat hippocampus of nimodipine group（ （ 369.75 ± 13.22）, （428.25 ± 17.69 ） respectively ） were higher than those of VD model group （ （ 142.25 ± 27.86 ）, （ 97.00± 5.88 ） , respectively ）, with difference of statistical significance （P 〈 0.01 ））. Conclusion Nimodipine can improve VD rats hippocampal neuronal injuries and their learning and memory impairment may be involved in the upregulating CREB and C/EBP DNA-binding activity.
出处
《中华行为医学与脑科学杂志》
CAS
CSCD
北大核心
2012年第6期518-520,共3页
Chinese Journal of Behavioral Medicine and Brain Science
基金
河北省人才工程培养项目（2010353）
河北省卫生厅医学科研重点课题（20090582）
