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

发布时间：2019-04-11 15:46

【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)(Aβ25-35)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(P0.05),血清HYD明显升高(P0.01),ACTH水平显著降低(P0.01),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(P0.05或P0.01),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。
[Abstract]:Objective To study the effect of Domenon on the hypothalamic-pituitary-adrenal axis (HPA) in rats with Alzheimer's disease (AD). Methods The AD model was prepared by intraventricular injection of P-amyloid (25-35) (A-25-35) and D-gal with D-gal in the lateral ventricle of male Wistar rats. The content of HPA-related hormone (HYD) and adrenocorticotropic hormone (ACTH) in rats were measured by radioimmunoassay. The expression of corticotropin-releasing hormone (CRH) and related receptor subtype 1 (CRH-R1) in the hypothalamus was observed by immunohistochemistry. The ultrastructure of the hypothalamus was observed by electron microscopy. Results Compared with the normal control group, the learning ability of the rats in the model control group decreased significantly (P0.05), the serum HYD was significantly higher (P0.01), the level of ACTH decreased significantly (P0.01), the expression of CRH and CRHR1 in the hypothalamus was reduced, the number of positive staining neurons was reduced, and the ultrastructure was changed. Compared with the model control group, the serum HYD decreased, ACTH gradually increased (P0.05 or P0.01), the expression of CRH and CRHR1 increased, and the ultrastructure of the hypothalamus was improved. Conclusion It can improve the function of HPA in AD rats and has a therapeutic effect on AD.
【作者单位】：潍坊医学院药理学教研室;潍坊医学院机能学实验室;
【基金】：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)
【分类号】：R965;R749.16

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