【摘要】：目的探討多奈哌齊對阿爾茨海默病(AD)模型大鼠下丘腦-垂體-腎上腺軸(HPA)的影響。方法健康雄性Wistar大鼠側(cè)腦室注射β-淀粉樣蛋白(25-35)(Aβ25-35)和腹腔注射D-半乳糖(D-gal)結(jié)合制備AD模型,隨機(jī)分為正常對照組、模型對照組、多奈哌齊組,每組10只。放射免疫測定大鼠HPA相關(guān)激素可的松(HYD)、促腎上腺皮質(zhì)激素(ACTH)含量,免疫組織化學(xué)法觀察下丘腦促腎上腺皮質(zhì)激素釋放激素(CRH)及相關(guān)受體亞型1(CRH-R1)的表達(dá),電鏡觀察下丘腦超微結(jié)構(gòu)。結(jié)果與正常對照組大鼠相比,模型對照組大鼠的學(xué)習(xí)能力明顯減退(P0.05),血清HYD明顯升高(P0.01),ACTH水平顯著降低(P0.01),下丘腦CRH和CRHR1表達(dá)減少,陽性染色神經(jīng)元數(shù)目減少,超微結(jié)構(gòu)呈損傷性改變。與模型對照組相比,多奈哌齊組大鼠血清HYD降低,ACTH逐漸升高(P0.05或P0.01),CRH和CRHR1表達(dá)增加,下丘腦超微結(jié)構(gòu)損傷改善。結(jié)論多奈哌齊能夠改善AD大鼠HPA功能,對AD具有治療作用。
[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.
【作者單位】： 濰坊醫(yī)學(xué)院藥理學(xué)教研室;濰坊醫(yī)學(xué)院機(jī)能學(xué)實(shí)驗(yàn)室;
【基金】：山東省高等學(xué)�？萍加媱濏椖�(J09LF81) 山東省優(yōu)秀中青年科學(xué)家科研獎勵基金(BS2010YY072) 山東省自然科學(xué)基金(ZR2010DM010;ZR2013HL069)
【分類號】：R965;R749.16

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