雌激素替代治疗阿尔茨海默病的机制:生后不同发育时期小鼠基底前脑内雌激素β受体的表达

目的研究出生后不同发育时期小鼠基底前脑内雌激素β受体( estrogen receptor β, ER-β)的表达,探讨雌激素替代治疗阿尔茨海默病( Alzheimer's disease, AD)的机制. 方法选择出生 0, 3, 7, 14 d, 1, 3, 12, 18个月的小鼠,每个时相点各 5只.动物前脑经多聚甲醛-丙烯醛混合固定液固定、冷冻切片后于一抗(兔抗 ER-β, sc-8 974)内孵育过夜,再行常规的免疫组化并用硫酸镍铵增强 DAB的显色. 结果小鼠基底前脑内 ER-β免疫阳性物质位于细胞核.新生时在两性基底前脑 ER-β免疫阳性细胞数目较少,生后第 14天～ 3月龄时最多,老年 (18月龄 )时表达显著减少甚至消失,尤其在雌性更明显. ER-β的表达具有一定的性别差异,表现为生后早期和老年时雄性表达强于同期雌性. 结论小鼠生后不同发育时期基底前脑内 ER-β蛋白的表达呈现弱-强-弱的变化模式,表明该受体可能参与了雌激素对基底前脑神经结构与功能的调节从而可能对 AD的发病产生影响,也可能是雌激素替代治疗 AD的重要机制.

Mechanism revealment of estrogen replacement therapy in Alzheimer's disease:the expression of estrogen receptor β in basal forebrain of mice at different growth stages after birth

AIM:To investigate the mechanism of estrogen replacement therapy(ERT) in Alzheimer's disease(AD) and the expression of estrogenic receptor β (ER-β ) in basal forbrain of mice at different growth stages after birth. METHODS:Mice,aged of 0,3,7 and 14 d and 1,3,12 and 18 month old, were selected with 5 cases of each period.Prosencephalon of the animal was fixed by paraformaldehyde-acrylaldehyde fixation liquid and incubated overnight in primary antibody after freezing slice,and then tested by routine immunohistochemistry as well as DAB coloration enhanced by nickel ammonium sulfate. RESULTS:ER-β immune reaction(IR) positive substance was situated in nuclei in basal forbrain of mice.The numbers of ER-β immune reaction positive cells were less in basal forbrain at neonatal stage of mice in both genders and with the most from the 14th day to 3 months after birth.The expressions decreased significantly even disappeared at its gerontism(18 months),especially in females. The expression of ER-β had a some difference in genders,which with stronger expressions at early and gerontism stage in males than females. CONCLUSION:The transformation mode of the expression of ER-β in basal forbrain at different stage after birth in mice is weak-strong-weak mode,which suggests that ER-β might participate in control process of estrogenic functions on neural structures and functions in basal forbrain,and therefore might affect the onset of AD as well as might be an important mechanism of estrogen replacement therapy in AD.