人参皂苷Rg1 抗衰老作用可能与改变p16 、cyclin D 、CDK4 的表达有关

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (1): 29-34.

人参皂苷Rg1 抗衰老作用可能与改变p16 、cyclin D 、CDK4 的表达有关

金建生, 赵朝晖, 陈晓春, 朱元贵, 曾育琦, 李永坤, 彭小松, 师广斌

福建医科大学附属协和医院、福建省老年医学研究所, 福州 350001, 福建

收稿日期:2003-06-26 修回日期:2003-07-18 出版日期:2004-01-26 发布日期:2020-11-16
通讯作者: 陈晓春,男, 教授, 博士生导师, 研究方向:神经系统变性疾病和衰老的分子机制。Tel:0591-3377664 E-mail:xc-chen329@sohu.com
作者简介:金建生, 女, 副教授, 硕士生导师, 研究方向:老年肾脏病和衰老的分子机制。
基金资助:
福建省自然科学基金项目(NO.C0210017)

Antiaging effect of ginsenoside Rg1 is related with the expression of p16,cyclin D1 and CDK4

JIN Jian-Sheng, ZHAO Chao-Hui, CHEN Xiao-Chun, ZHU Yuan-Gui, ZHENG Yu-Qi, LI Yong-Kun, PENG Xiao-Song, SHI Guang-Bin

The Affiliated Union Hospital, Fujian Medical University &Fujian Institute of Geriatric Medicine, Fuzhou 350001, Fujian, China

Received:2003-06-26 Revised:2003-07-18 Online:2004-01-26 Published:2020-11-16

摘要/Abstract

摘要： 目的: 探讨人参皂苷Rg1 对抗三丁基过氧化氢(t-BHP) 诱导的WI-38 细胞衰老作用及其可能细胞周期调控机制。方法: 将WI-38 细胞随机分为4组, 用不同剂量Rg1 预处理。从30 代开始, 隔代用t-BHP 作用, 每次1 h, 共4 次, 诱导细胞衰老。从光镜、透射电镜观察细胞形态及超微结构;流式细胞术分析G₁期细胞比例;以及SA-β-半乳糖苷酶的细胞化学染色, 确定Rg1 的抗衰老作用。并采用免疫印迹技术对CDK4 、cyclin D1 和p16 等表达情况进行检测。结果: Rg1 预处理组与单纯t-BHP 处理组相比,细胞形态体积小、胞体不如后者扁平, 次级溶酶体减少,G₁ 期细胞比例下降, SA-β-半乳糖苷酶染色阳性细胞百分比下降, 说明Rg1 在t-BHP 诱导细胞衰老模型中有抗衰老作用。进一步发现用Rg1 预处理后, p16 、cyclin D1 表达水平降低、CDK4 表达水平增加。结论: 提示Rg1 可能通过改变细胞周期调控因子的表达而发挥其抗t-BHP 诱导的WI-38 细胞衰老作用。

关键词: 人参皂苷Rg1, p16, cyclin D, CDK4, 衰老, 三丁基过氧化氢

Abstract: AIM: To investigate the antiaging effects of ginsenoside Rg1 and the possible mechanism of cell cycle in senescence model induced by tert-butylhydroperoxide (t-BHP).METHODS: WI-38 cells were divided into 4 groups and randomly added with different concentrations of Rg1.From 30 population doubling (PD), WI-38 cells were exposed to t-BHP for 1 h at every two PDs. Four stresses were induced to reach premature senescence.The changes of cells of were observed by microscope and flow cytometric assay, and the SA-β-galactosidase staining was used to investigate the antiaging effect of ginsenoside Rg1.The expression of CDK4, cyclin D1 and p16 was detected by Western blot.RESULTS: Cells of Rg1 groups were smaller and less flat than those in the group only treated with t-BHP. In addition, the number of secondary lysosome, cells in G₁ phase, and activity of β-galactosidase decreased.Futhermore it showed higher expression of CDK4 and lower expression of cyclin D1 and p16 in comparison with cells only treated with t-BHP.CONCLSION: The possible mechanism of antiaging effect of Rg1 is to regulate the expression of p16, cyclin D1 and CDK4 In senescence model induced by t-BHP.

Key words: ginsenoside Rg1, p16, cyclin D, CDK4, senescence, tert-butylhydroperoxide

中图分类号:

R285.5

金建生, 赵朝晖, 陈晓春, 朱元贵, 曾育琦, 李永坤, 彭小松, 师广斌. 人参皂苷Rg1 抗衰老作用可能与改变p16 、cyclin D 、CDK4 的表达有关[J]. 中国临床药理学与治疗学, 2004, 9(1): 29-34.

JIN Jian-Sheng, ZHAO Chao-Hui, CHEN Xiao-Chun, ZHU Yuan-Gui, ZHENG Yu-Qi, LI Yong-Kun, PENG Xiao-Song, SHI Guang-Bin. Antiaging effect of ginsenoside Rg1 is related with the expression of p16,cyclin D1 and CDK4[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(1): 29-34.

参考文献

1 Ohtani N, Zebedee Z, Huot TJ, et al. Opposing effects of Ets and Id proteins on p16INK4a expression during cellular senescence[J]. Nature, 2001;409:1067-70
2 Zhang JT.AF150(S) and AF267B:M1 muscarinic agonists as innovative therapies for Alzheimer' s disease[J]. J Mol Neurosci, 2002;19:145-53
3 Cockcroft VG, Ross G JB, Peddemors VM.Distribution and status of bottle-nosed-dolphin tursiops truncatus on the south coast of Natal, South Africa[J]. South Afri J Marine, 1991;11:203-9
4 Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo[J]. Proc Natl Acad Sci USA, 1995;92:9363-7
5 Chen XC, Zhu YG, Wang XC.Protective effect of ginsenoside Rg1 on dopamine-induced apoptosis in PC12 cells[J]. Acta Pharmacol Sin, 2001;22:673-8
6 Sherr CJ.G₁ phase progression:cycling on cue[J]. Cell, 1994;79:551-5
7 Lee JY, Bielawska AE, Obeid LM.Regulation of cyclin-dependent kinase 2 activit y by ceramide[J]. Exp Cell Res, 2000;261:303-11
8 Sandhu C, Peehl DM, Slingerland J.p16INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells[J]. Cancer Res, 2000;60:2616-22
9 Sandhu C, Donovan J, Bhattacharya N, et al. Reduction of Cdc25A contributes to cyclin E1-Cdk2 inhibition at senescence in human mammary epithelial cells[J]. Oncogene, 2000;19:5314-23
10 Lucibello FC, Sewing A, Brusselbach S, et al. Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent humanfibroblasts[J]. J Cell Sci, 1993;105(Pt 1):123-3
11 Brown JP, Wei W, Sedivy JM.Bypass of senescence after disruption of p21CIP1 WAF1 gene in normal diploid human fibroblasts[J]. Science, 1997;277:831-4
12 Dulic V, Beney GE, Frebourg G, et al. Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts[J]. Mol Cell Biol, 2000;20:6741-54.
13 Sandhu C, Donovan J, Bhattacharya N, et al. Reduction of Cdc25A contributes to cyclin E1-Cdk2 inhibition at senescence in human mammary epithelial cells[J]. Oncogene, 2000;19:5314-23
14 Lucibello FC, Sewing A, Brusselbach S, et al. Deregulation of cyclins D1 and E and suppression of cdk2 and cdk4 in senescent human fibroblasts[J]. J Cell Sci, 1993;105(Pt 1):123-33
15 Sandhu C, Peehl DM, Slingerland J.p16INK4A mediates cyclin dependent kinase 4 and 6 inhibition in senescent prostatic epithelial cells[J]. Cancer Res, 2000;60:2616-22

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