长期口服雌激素或复方雌激素对去卵巢大鼠海马结构内β-淀粉样蛋白沉积的影响

Effects of long-term replacement therapy of estrogen or compound estrogen on the deposition of beta-amyloid protein in OVX rat hippocampal formation

目的观察长期口服雌激素或复方雌激素对去卵巢大鼠大脑海马结构内β-淀粉样蛋白(Aβ)沉积的影响。方法7月龄SD大鼠随机分成5组:正常对照组、假手术组、去卵巢组、17β-雌二醇预防干预组(雌二醇干预组)和复方尼尔雌醇预防干预组(尼尔雌醇干预组)。去卵巢组、雌二醇干预组及尼尔雌醇干预组手术切除卵巢,并分别对雌二醇干预组及尼尔雌醇干预组饲喂相应的药物35周,处死各组大鼠,用免疫组化法、细胞计数及图像分析观察各组大鼠海马结构内Aβ沉积的变化。结果去卵巢组海马结构内各亚区Aβ阳性神经元数量和平均光密度明显高于其他4组(均P<0·05)。结论长期雌激素缺乏导致大鼠海马结构内Aβ沉积增加,减少Aβ的沉积可能是雌激素神经保护的重要机制之一,雌激素与复方雌激素效果相同。

Objective To investigate the effects of long-term replacement therapy of estrogen or compound estrogen on the deposition of beta-amyloid protein （Aβ） in ovariectomy （OVX） rat hippocampal formation. Methods Fifty seven-month-old female Sprague-Dawley rats were randomly divided into five groups： normal control, SHAM, OVX, OVX plus 17beta-estradiol （OVX/ERT）, and OVX plus compound nylestriol tablet （OVX/NL）. The ovariectomy was performed in OVX, OVX/NL and OVX/ERT rats and drugs were administered orally in OVX/NL and OVX/ERT rats for 35 weeks after the ovariectomy. Then the rats in all groups were sacrificed. Immunohistochemistry of Aβ, cell counting and imaging system were used to determine the change of Aβ deposition levels in OVX rat hippocampal formation. Results The numbers and optical density of Aβ-positive neurons of all hippocampal subreglons and dentate gyrus in OVX rats were markedly higher than those of normal control, SHAM ,OVX/NL, and OVX/ERT rats （P 〈 0. 05 ）, but there were no differences in Aβ-positive neurons among normal control, SHAM, OVX/NL and OVX/ERT rats. Conclusions Long-term estrogen deficiency results in an increase of deposition of Aβ. Replacement of estrogen or compound estrogen can equally inhibit the deposition of Aβ in hippocampal formation, which may be mainly neuroprotective mechanism of estrogen.