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雌二醇对大鼠皮质原代神经元α分泌酶活性的影响 被引量:5

Effects of 17β-estradiol on α-secretase activity in rat cortical neurons
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摘要 目的:探讨雌二醇对α分泌酶活性的影响及其可能机制。方法:雌二醇作用于大鼠皮质神经元8h,采用MTT法检测其对细胞活力的影响,应用荧光法检测其对α分泌酶活性的影响,应用Western Blot检测其对可溶性淀粉样前体蛋白(sAPPα)分泌的影响;并检测丝裂原活化的蛋白激酶(MAPK)抑制剂PD98059对雌二醇引起的α分泌酶活性的影响和各种条件下雌二醇对磷酸化和非磷酸化的MAPK活性的影响。结果:1~500μmol/L雌二醇对大鼠皮质神经元细胞活力无明显影响(F=2.101,P>0.05),但其可呈剂量依赖性地增加α分泌酶的活性(F=10.368,P<0.05),其中100μmol/L的雌二醇可使α分泌酶活性增加至对照组的(150.4±15.1)%(P<0.05)。1~100μmol/L的雌二醇均促进sAPPα的分泌(F=86.360,P<0.05),100μmol/L的雌二醇使sAPPα分泌增加至对照组的(270.5±25.6)%(P<0.05)。与雌二醇相比,加入PD98059后α分泌酶活性降至(124.1±13.5)%(F=43.699,P<0.05)。100μmol/L的雌二醇使磷酸化MAPK的活性增加至对照组的(160.6±18.3)%(P<0.05),此种作用能被PD98059部分拮抗(120.8±15.5)%(F=22.700,P<0.05);在各种条件下,对非磷酸化MAPK的活性无明显影响(F=2.063,P>0.05)。结论:雌二醇可以增加α分泌酶活性,而激活MAPK可能是其增加α分泌酶活性的机制之一。 Aim:To investigate the effects of 17β-estradiol on α-secretase activity and the possible mechanisms.Methods:17β-estradiol was added to primary rat cortical neurons and its effect on cell viability,α-secretase activity and sAPPα secretion were detected. The effect of mitogen activated protein kinase (MAPK) inhibitor PD98059 on 17β-estradiol-induced α-secretase activity alternation were also measured. Then the phosphorylated MAPK and nonphosphorylated MAPK activities after 17β-estradiol treatment were analyze...
出处 《郑州大学学报(医学版)》 CAS 北大核心 2009年第5期999-1003,共5页 Journal of Zhengzhou University(Medical Sciences)
关键词 雌二醇 α分泌酶 丝裂原活化的蛋白激酶 阿尔茨海默病 大鼠 estradiol α-secretase mitogen activated protein kinase Alzheimer’s disease rat
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