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浙江大学学报（医学版）
浙江大学学报（医学版）  2012, Vol. 41 Issue (4): 393-401    DOI: 10.3785/j.issn.1008-9292.2012.04.007
专题报道     
人参皂苷Rg1经线粒体通路抗Aβ25-35致原代大鼠皮层神经元凋亡
吴佳莹1，沈圆圆2，朱闻杰1，程梅园1，王志强1，刘琰1，朱丹雁1，楼宜嘉1
1．浙江大学 药学院 心脑血管与肝脏药理研究室，浙江 杭州 310058； 2.浙江大学医学院 附属第二医院脑重症医学科，浙江 杭州 310009
Ginsenoside Rg1 antagonizes β-amyloid peptide-induced apoptosis in primarily cultured rat neurons via mitochondrial pathway
WU Jia-ying1, SHEN Yuan-yuan2, ZHU Wen-jie1, CHENG Mei-yuan1, WANG Zhi-qiang1, LIU Yan1, ZHU Dan-yan1, LOU Yi-jia1
1.Institution of Pharmacology, Toxicology and Biological Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; 2.Department Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
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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、20 μmol/L Rg1预处理24 h，加入Aβ毒性片段Aβ25-35 10 μmol/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（20 μmol/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1 μmol/L至20 μmol/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。
关键词： 大脑皮质/病理学； 神经元/药物作用； 细胞凋亡/药物作用； 人参皂苷/药理学； 人参皂苷Rg1； 原代皮层神经元； 神经保护； β  淀粉样肽； 细胞凋亡； 线粒体    
Abstract: Objective： To assess the neuroprotective effects of ginsenoside Rg1 against β-amyloid peptide (Aβ25-35) -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 Aβ25-35 for 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 Aβ25-35 for 72 h caused serious neural cell insults. A pretreatment with Rg1 significantly reduced Aβ25-35-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 Aβ25-35 treatment, while Rg1 maintained the normal level of ΔΨm. A series of mitochondrion-mediated apoptotic events happened after Aβ25-35 treatment, 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 Aβ25-35-induced injury, which may be associated with mitochondrion-mediated antiapoptosis pathway.
Key words: Cerebral cortex/pathol    Neurons/drug eff    Apoptosis/drug eff    Ginsenoside/parmacol    Ginsenoside Rg1； Primary cultured cortical neurons； Neuroprotection； Aβ； Apoptosis； Mitochondrion
出版日期: 2012-07-25
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引用本文:

吴佳莹;沈圆圆;朱闻杰;程梅园;王志强;刘琰;朱丹雁;楼宜嘉. 人参皂苷Rg1经线粒体通路抗Aβ25-35致原代大鼠皮层神经元凋亡[J]. 浙江大学学报（医学版）, 2012, 41(4): 393-401.

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https://www.zjujournals.com/med/CN/Y2012/V41/I4/393

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