雌激素缺失及17β-estradiol替代治疗对大鼠海马β淀粉样蛋白含量的影响  

Effect of estrogen-depletion and 17β-estradiol replacement therapy upon rat hippocampus β-amyloid generation

作　　者：杨红旗[1] 孙治坤[1] 蒋秋焕[1] 尚茜[1] 徐军[1] 

机构地区：[1]河南省人民医院神经内科,郑州450003

出　　处：《中华医学杂志》2009年第37期2658-2661,共4页National Medical Journal of China

摘　　要：目的观察雌激素缺失及雌二醇（17β-estradiol）替代治疗对大鼠海马B淀粉样蛋白（Aβ）含量的影响及其可能机制。方法切除大鼠双侧卵巢制作雌激素缺失模型（Ovx），然后给予17β-estradiol补充治疗。ELISA检测海马Aβ含量，荧光法测定α和β分泌酶活性，Western印迹检测β分泌酶（BACE1）和中性内肽酶（NEP）的表达。结果Ovx大鼠雌激素水平[（11±4）pg／ml，P〈0．01]明显低于对照组[（21±8）pg／m1]，而给予17β-estradiol替代治疗后雌激素水平上升[（63±13）pg／ml，P〈0．01]；Ovx大鼠海马组织Aβ40[（28．5±4．5）ng／ml，P〈0．01]和Aβ42含量[（4．6±1．2）ng／ml，P〈0．01]均显著高于对照组的Aβ40[（14．4±2．4）ng／ml]和Ap42[（2．8±0．4）ng／ml]；而17β-estradiol替代治疗可以使Ap40[（20．3±3．2）ng／ml，P〈0．01]和AB42[（3．8±0．5）ng／ml，P〈0．01]降低；Ovx大鼠01分泌酶活性降低（67．5％，P〈0．01）而B分泌酶活性增加（145．8％，P〈0．01），17β-estradiol替代治疗后部分逆转了上述现象；Ovx大鼠BACE1的表达增加（135．4％，P〈0．01）而NEP表达降低（40．8％，P〈0．01），而补充17β-estradiol后可以部分拈抗上述作用。结论雌激素缺失可以增加去势大鼠海马AB含量，这可能与α分泌酶活性下降、BACE1活性增加和（或）NEP活性下降有关，而补充17β-estradiol可以降低Aβ含量；这可能是绝经后妇女雌激素替代治疗降低阿尔茨海默病发病危险性的原因之一。Objective To observe the effects of estrogen depletion and 17β-estradiol replacement therapy upon ratβ-amyloid （Aβ） generation and the possible related mechanisms. Methods Rat ovaries were ectomized to mimic estrogen-depletion models and then 17β-estradiol was administered by powdering hormone into soy-free chow as a way of replacement therapy. ELISA was carried out to detect rat hippoeampus Aβ levels and α- and β-secretase activities were measured after the experiment. The effects of estrogen depletion and 17β-estradiol replacement therapy upon β-seeretase （BACE1） and neprilysin （NEP） expression were also analyzed by Western blot. Results Ovarieetomy significantly decreased estrogen level [ （11 - 4） pg/ml, P 〈 0. 01 ] as compared with control group [ （21 ± 8） pg/ml while 17β-estradiol administration increased the estrogen level [ （63 ±13） pg/ml, P 〈0. 01] in blood. The A1540 [ （28.5± 4. 5） ng/ml, P 〈 0. 01 ] and Aβ42 [ （4. 5 ± 1.2 ） ng/ml, P 〈 0. 01 ] levels were higher in ovariectomy group as compared with their respective control group [ with AI340 （ 14.4 ± 2. 4 ） ng/ml and A1342 （2. 8 ± 0.4） ng/ml respectively]. But the effects of ovariectomy on A13 content can be partially reversed by 17β- estradiol replacement therapy [ with Aβ40 （ 20. 3 ± 3.2 ） ng/ml, P 〈 0. 01 and Aβ42 （ 3.8 ± 0. 5 ） ng/ml, P 〈 0. 01 respectively ] . Estrogen depletion decreased α-seeretase activity （ 67.5% , P 〈 0. 0l ） and increased β-secretase activity （ 145. 8%, P 〈 0. 01 ） and this effect can be blocked by 17β-estradiol administration [ with α-secretase activity to 90. 2% （ P 〈 0. 01 ） and β-secretase activity to 92.4% （ P 〈 0. 01 ） ]. Ovariectomy increased BACEI expression （ 135.4% , P 〈 0. 01 ） and decreased NEP expression （40. 8%, P 〈 0. 01 ） and this effect can be partially antagonized by 17β-estradiol supplementary [ with BACE to 103.5% （P〈0.01） and NEP to 88.4% （P〈0.01）]. Conclusion Estrogen de

关 键 词：雌激素类 淀粉样Β蛋白 α分泌酶 Β分泌酶 中性内肽酶 阿尔茨海默 

分 类 号：R686[医药卫生—骨科学]