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α硫辛酸对阿尔茨海默病模型大鼠海马区CREB、Bcl-2表达的影响

Effect of alpha-lipoic acid on CREB and Bcl-2 expression in the hippocampus of Alzheimer's disease model rats
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摘要 目的观察α硫辛酸对阿尔茨海默病模型大鼠海马区cAMP反应元件结合蛋白(p-CREB)、B淋巴细胞瘤-2(Bcl-2)表达的影响。方法将24只清洁级SD雄性大鼠随机分为假手术组、模型组、α硫辛酸组,每组各8只。采用双侧海马一次性注射Aβ1-42的方法在模型组及α硫辛酸组中建立AD大鼠模型。同时α硫辛酸组给予腹腔注射α硫辛酸100 mg/(kg·d)。采用Morris水迷宫实验观察大鼠空间记忆能力,HE染色观察大鼠海马区锥体细胞的形态学变化,同时采用Western Blot方法检测各实验组大鼠脑海马组织中p-CREB,Bcl-2蛋白表达情况。结果 Morris水迷宫测试显示AD模型大鼠的学习记忆能力的明显下降,经α硫辛酸治疗的AD模型大鼠学习记忆得到改善。HE染色显示,AD模型组海马CAl区锥体细胞数量明显减少,排列稀疏,结构紊乱;α硫辛酸组大鼠海马数量和形态均不同程度恢复。AD模型组中大鼠海马组织中p-CREB,Bcl-2蛋白水平较假手术组明显降低(P<0.01);给予α硫辛酸干预后大鼠海马p-CREB,Bcl-2蛋白水平较模型组明显增多(P<0.01)。结论α硫辛酸能够提高AD模型大鼠的学习记忆能力,可能是通过CREB-Bcl-2信号通路的活化来实现的。 Objective To study the effect of alpha-lipoic acid on p-CREB and Bcl-2 expression in the hippocampus of Aβ1-42-induced alzheimer's disease model rats.Methods SD rats were randomly divided into sham-operated group,model group,alpha-lipoic acid group,with 8 rats in each group.Bilateral hippocampus were injected condensed Aβ1-42 to establish rat model of AD.We used Morris water maze to test rats' incubation period and to observe the influence of alpha-lipoic acid treatment in incubation period of rats.Through the HE staining,the morphological changes of pyramidal cells in the hippocampal area were observed.The expression levels of p-CREB and Bcl-2 in the hippocampus of rats in different groups were detected by Western blot technique.Results Morris water maze test showed that the terms of learning and memory in AD model rats decreased obviously,but they were improved by the alpha-lipoic acid treatment.Compared with the sham-operated group,the expression levels of p-CREB and Bcl-2 in the hippocampus of model group were decreased significantly( P〈0.01).Compared with model group,the expression levels of p-CREB and Bcl-2 in the hippocampus of rats of alpha-lipoic acid group were enhanced significantly( P 〈0.01).Conclusions Alpha-lipoic acid improves the learning and memory ability of AD model rats probably by the activation of CREB-Bcl-2 signal path.
作者 杨丽萍 凌书建 李国祥 李秀英 申向辉 YANG Li-ping, LING Shu-fian, LI Guo-xiang, LI Xiu-ying, SHEN Xiang-hui.(Department of Critical Care Medicine, Central Hospital of Handan, handan 056007, Chin)
出处 《实用老年医学》 CAS 2018年第3期214-217,共4页 Practical Geriatrics
关键词 阿尔茨海默病 CAMP反应元件结合蛋白 Bcl-2 Α硫辛酸 Alzheimer's disease p-CREB Bcl-2 alpha-lipoic acid
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