摘要
目的:探讨依达拉奉(MCI-186)保护阿尔茨海默病海马神经元的机制。方法:采用穹隆海马伞切断联合侧脑室注射β淀粉样蛋白25-35(Aβ25-35)方法建立阿尔茨海默病大鼠动物模型;将Wistar雄性大鼠分为5组:正常对照组、假手术组、痴呆组、大剂量和小剂量依达拉奉治疗组;采用Morris水迷宫法,进行定位航行实验和空间探索实验,于第7天和第24天分别测定大鼠找到平台所需时间(即逃避潜伏期)和2 min内跨越原平台所在位置的次数,进行学习、记忆能力测定;于第28天分离海马组织,HE染色后光镜下观察海马CA1区神经元形态学变化,在TUNEL染色后计算凋亡指数(阳性细胞数/总细胞数×100%)以及利用蛋白质印迹法检测NF-κB P65和Caspase-3 P20蛋白的表达。结果:与正常对照组和假手术组相比,第7天痴呆组大鼠逃避潜伏期明显延长、跨越平台次数明显减少(P<0.01);海马CA1区存在着大量脱失的神经元,细胞排列稀松、不规则;凋亡指数增加、NF-κB P65和Caspase-3 P20蛋白相对表达量增多(P<0.01)。与痴呆组相比,依达拉奉治疗组第24天大鼠逃避潜伏期明显缩短、跨越平台次数明显增多(P<0.01),海马CA1区神经元接近正常,细胞排列紧密、规则;凋亡指数降低,NF-κB P65和Caspase-3 P20蛋白相对表达量减少,尤以小剂量组改变更明显(P<0.01);但与正常对照组相比,差异有统计学意义(P<0.01)。结论:依达拉奉能够通过抑制细胞凋亡途径在阿尔茨海默病治疗中发挥重要作用。
Objective: To determine protective effect of MCI-186(edaravone) on hippocampal neurons in Alzheimer′s disease(AD).Methods: Hippocampal fimbria-fornix disconnexion combined with Aβ25-35 injection intraventricular was used to establish rat model of AD.Wistar rats were respectively divided into five groups: normal,sham-operation,dementia,low-dose MCI-186 treatment and high-dose MCI-186 treatment.The escape latency and the spanning platform times within 2 minutes were respectively determined by Morris water maze at the 7th and 24th day to detect the ability of learning and memory in each group.Cerebral tissue in hippocampal CA1 region was dissociated at the 28th day.Morphology of neurons in this region was observed by H&E staining,apoptosis index was calculated after TUNEL analysis and expressions of NF-κB P65 and Caspase-3 P20 were detected by Western blot.Results: Compared with normal control group and sham-operation group,the escape latency significantly prolonged but the spanning platform times decreased at the 7th day(P<0.01),there were lots of degenerative neurons and sparse irregular cell arrangements in hippocampal CA1 region,and not only apoptosis index,but also relative expressions of NF-κB P65 and Caspase-3 P20 went up in the dementia group(P<0.01).When the rats were given MCI-186,the escape latency shortened,while the spanning platform times increased on 24th day(P<0.01 or P<0.05),and the degenerative neurons significantly decreased,cell arrangement became close and regular,apoptosis index decreased,and relative expressions of NF-κB P65 and Caspase-3 P20 also went down(P<0.01),especially in the low-dose MCI-186 group.Conclusion: MCI-186 plays a certain role in the treatment of AD through inhibiting cell apoptosis.
出处
《江苏大学学报（医学版）》
CAS
2011年第3期194-198,180,共6页
Journal of Jiangsu University：Medicine Edition
基金
黑龙江省自然科学基金资助项目(D200807)
江苏大学临床医学科技发展基金资助项目(JLY20080013)
