中文摘要：

目的：通过人参皂苷Rg1与原代培养大鼠皮层神经元预培养,评价抗β淀粉样肽（β-amyloid peptide,Aβ）所致神经元损伤,并探讨Rg1的神经保护作用及相关分子机制。方法：原代神经元培养7 d成熟后,分别以1、10、20μmol/L Rg1预处理24 h,加入Aβ毒性片段Aβ25-3510μmol/L模拟阿尔茨海默病（Alzheimer＇s Disease,AD）脑组织局部微环境。孵育72 h后,光镜观察细胞形态学改变,评价Rg1是否具有神经保护作用及相关量效关系。采用JC-1染色,考察神经元线粒体膜电位（ΔΨm）变化,并运用Western blot技术,检测凋亡相关蛋白的表达变化。结果：Aβ25-35作用72 h严重损伤原代皮层神经元,引起神经元碎裂和死亡。Rg1预处理能对抗Aβ25-35的细胞损伤作用,显著提高神经元存活率,并呈现剂量依赖性,其中Rg1（20μmol/L）活性最强。Aβ25-35处理24 h能降低神经元的线粒体ΔΨm,下调Bcl-2/Bax的比值,引起细胞色素c从线粒体释放入胞浆,活化caspase 3和caspase 9,从而引起神经元凋亡。而Rg1预培养能保护原代神经元,减轻或避免上述损伤作用,且其抗凋亡效应可被雌激素受体（ER）拮抗剂ICI182,780和糖皮质激素受体（GR）拮抗剂RU486部分拮抗。结论：Rg1在1μmol/L至20μmol/L浓度具有抗Aβ25-35损伤原代培养大鼠皮层神经元作用,该活性与抑制线粒体凋亡通路相关联。

英文摘要：

Objective： To assess the neuroprotective effects of ginsenoside Rg1 against β-amyloid peptide（Aβ 25-35）-induced apoptosis in primarily cultured rat cortical neurons. Methods： Primarily cultured cortical neurons were obtained from embryonic（E18d） rat fetus and maintained in neurobasal medium for 7d.Primary neurons pretreated with 1 μmol/L,10 μmol/L or 20 μmol/L Rg1 for 24 h were challenged with 10 μmol/L Aβ 25-35for 72 h.Morphological changes of neurons were evaluated;mitochondrial membrane potential（ΔΨm） was measured;with JC-1 staining and the expression of neural apoptosis-related proteins was detected by Western blot analysis. Results： Exposure to Aβ 25-35for 72 h caused serious neural cell insults.A pretreatment with Rg1 significantly reduced Aβ 25-35-induced cell death in a dose-dependent manner,with a maximal effect（-90%） obtained at 20 μmol/L.The JC-1 staining results demonstrated the loss of ΔΨm after Aβ 25-35treatment,while Rg1 maintained the normal level of ΔΨm.A series of mitochondrion-mediated apoptotic events happened after Aβ 25-35treatment,such as decrease of Bcl-2/Bax,release of cytochrome C and activation of caspase 9 and caspase 3,which were all blocked by Rg1 pretreatment.Both estrogen receptor（ER） antagonist ICI182,780 and glucocorticoid receptor（GR） antagonist RU486 blocked the antiapoptotic effects of Rg1. Conclusions： Ginsenoside Rg1 protects primary cultured rat cortical neurons from Aβ 25-35-induced injury,which may be associated with mitochondrion-mediated antiapoptosis pathway.