多奈哌齐对阿尔茨海默病模型大鼠下丘脑-垂体-肾上腺轴的影响

doi:10.6040/j.issn.1671-7554.0.2014.010

山东大学学报（医学版） ›› 2014, Vol. 52 ›› Issue (7): 11-15.doi: 10.6040/j.issn.1671-7554.0.2014.010

多奈哌齐对阿尔茨海默病模型大鼠下丘脑-垂体-肾上腺轴的影响

王金红¹, 李文涛², 于树田¹, 董丽¹

1. 潍坊医学院药理学教研室, 山东潍坊 261053;
2. 潍坊医学院机能学实验室, 山东潍坊 261053

收稿日期:2014-01-06 修回日期:2014-06-10 出版日期:2014-07-10 发布日期:2014-07-10
通讯作者: 王金红。E-mail：wfmcwjh@wfmc.edu.cn E-mail:wfmcwjh@wfmc.edu.cn
基金资助:
山东省高等学校科技计划项目（J09LF81）；山东省优秀中青年科学家科研奖励基金（BS2010YY072）；山东省自然科学基金（ZR2010DM010；ZR2013HL069）

Effect of donepezil on hypothalamic-pituitary-adrenocortical-axis in Alzheimer’s disease rats

WANG Jinhong¹, LI Wentao², YU Shutian¹, DONG Li¹

1. Department of Pharmacology, Weifang Medical University, Weifang 261053, Shandong, China;
2. Department of Functional Laboratory, Weifang Medical University, Weifang 261053, Shandong, China

Received:2014-01-06 Revised:2014-06-10 Online:2014-07-10 Published:2014-07-10

摘要/Abstract

摘要： 目的探讨多奈哌齐对阿尔茨海默病（AD）模型大鼠下丘脑-垂体-肾上腺轴（HPA）的影响。方法健康雄性Wistar大鼠侧脑室注射β-淀粉样蛋白（25-35）（Aβ_25-35）和腹腔注射D-半乳糖（D-gal）结合制备AD模型，随机分为正常对照组、模型对照组、多奈哌齐组，每组10只。放射免疫测定大鼠HPA相关激素可的松（HYD）、促肾上腺皮质激素（ACTH）含量，免疫组织化学法观察下丘脑促肾上腺皮质激素释放激素（CRH）及相关受体亚型1（CRH-R1）的表达，电镜观察下丘脑超微结构。结果与正常对照组大鼠相比，模型对照组大鼠的学习能力明显减退（P<0.05），血清HYD明显升高（P<0.01），ACTH水平显著降低（P<0.01），下丘脑CRH和CRHR1表达减少，阳性染色神经元数目减少，超微结构呈损伤性改变。与模型对照组相比，多奈哌齐组大鼠血清HYD降低，ACTH逐渐升高（P<0.05或P<0.01），CRH和CRHR1表达增加，下丘脑超微结构损伤改善。结论多奈哌齐能够改善AD大鼠HPA功能，对AD具有治疗作用。

关键词: 多奈哌齐, 促肾上腺皮质激素释放激素, 阿尔茨海默病模型大鼠, 促肾上腺皮质激素, 可的松

Abstract: Objective To investigate the effect of donepezil on hypothalamic-pituitary-adrenocortical-axis(HPA)in Alzheimer's disease (AD) rats. Methods A total of 30 healthy male Wistar rats were injected into amyloid β-protein 25-35 (Aβ_25-35) intracerebroventricularly and D-galactose (D-gal) intraperitoneally to prepare AD model and divided into normal control group, AD model group, and donepezil group randomly, and 10 rats in each group. Serum hydrocortisone (HYD) and adrenocorticotropic hormone (ACTH) concentrations were detected by radioimmunoassay. Morphology of hypothalamus was observed with transmission electron microscope, and the expressions of corticotropin releasing hormone (CRH) and CRH receptor 1 (CRHR1) were observed by immunohistochemical method. Results Compared with normal control group, learning ability of model rats decreased (P<0.05), HYD concentration increased (P<0.01), ACTH concentration decreased significantly (P<0.01), and the expressions of CRH and CRHR1 reduced. The ultrastructure of hypothalamus of model rats were damaged. Compared with AD model group, donepezil decreased serum concentration of HYD and increased serum concentration of ACTH in the AD rats (P<0.05 or P<0.01 respectively), and improved the expressions of CRH and CRHR1, which protected ultrastructure damage of hypothalamus. Conclusion Donepezil improves the function of HPA in AD rats and shows treatment effect on AD.

Key words: Donepezil, Adrenocorticotropic hormone, Alzheimer’s disease rats, Corticotropin releasing hormone, Hydrocortisone

中图分类号:

R574

王金红, 李文涛, 于树田, 董丽. 多奈哌齐对阿尔茨海默病模型大鼠下丘脑-垂体-肾上腺轴的影响[J]. 山东大学学报（医学版）, 2014, 52(7): 11-15.

WANG Jinhong, LI Wentao, YU Shutian, DONG Li. Effect of donepezil on hypothalamic-pituitary-adrenocortical-axis in Alzheimer’s disease rats[J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2014, 52(7): 11-15.

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多奈哌齐对阿尔茨海默病模型大鼠下丘脑-垂体-肾上腺轴的影响

Effect of donepezil on hypothalamic-pituitary-adrenocortical-axis in Alzheimer’s disease rats

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