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水飞蓟素对雷帕霉素诱导的内皮祖细胞凋亡和生长抑制的拮抗作用

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第4期
页码:
393-399
栏目:
基础研究
出版日期:
2013-07-25

文章信息/Info

Title:
Protective effect of silymarin against rapamycininduced apoptosis and proliferation inhibition in endothelial progenitor cells
作者:
张 鹏1; 乔 昆2; 任雨笙3; 梁 春3; 冷 冰3; 吴宗贵3
(1.解放军第273医院心内科，新疆 库尔勒 841000；2.兰州大学心理学教研室，甘肃 兰州 730000；3.第二军医大学附属长征医院心内科，上海 200003)
Author(s):
ZHANG Peng1;  QIAO Kun2;  REN Yusheng3;  LIANG chun3;  LENG Bing3;  WU Zong gui3
(1.Department of Cardiology, PLA 273 Hospital, Korla 841000, Xinjiang, China; 2.Department of Psychology, Lanzhou University, Lanzhou 730000, Gansu, China; 3.Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China)
关键词:
内皮祖细胞; 雷帕霉素; 水飞蓟素; 增殖; 抑制; 细胞凋亡
Keywords:
endothelial progenitor cells;  rapamycin;  silymarin;  proliferation;  migration;  apoptosis;  angiogenesis
分类号:
R284.1
DOI:
-
文献标识码:
A
摘要:
目的:水飞蓟素对雷帕霉素诱导的内皮祖细胞（EPCs）凋亡和生长抑制的拮抗作用。方法:通过密度梯度离心法分离、培养、鉴定得到EPCs；在EPCs培养物中加入不同浓度（0、01、1、10、100 ng/ml）的雷帕霉素干预24 h和加入（1 ng/ml）雷帕霉素干预不同时间（0 、6、12、24、48 h）。收集细胞检测其增殖和迁移能力。在EPCs培养物中加入不同浓度（0、25、50、100 μg/ml）的水飞蓟素干预24 h后，收集细胞检测其增殖、迁移和凋亡的水平。在EPCs培养物中同时加入（1 ng/ml）雷帕霉素和不同浓度（25、50、100 μg/ml）水飞蓟素干预24 h后，收集细胞检测其增殖、迁移、凋亡和体外血管生成的能力。结果:与未药物干预的EPCs培养物相比较，雷帕霉素（1、10、100 ng/ml）能抑制EPCs增殖和迁移，并随干预浓度的增加和干预时间的延长而增加（P<0.05）。水飞蓟素干预24 h后，50 μg/ml和100 μg/ml的水飞蓟素可明显增加EPCs增殖和迁移的能力（P<0.05），25~100 μg/ml的水飞蓟素可明显抑制EPCs凋亡（P<005），并呈浓度依赖性。EPCs在加入雷帕霉素（1 ng/ml）和不同浓度水飞蓟素（25、50、100 μg/ml）共同干预24 h后，50 μg/ml和100 μg/ml的水飞蓟素都可明显改善雷帕霉素对EPCs的促凋亡作用，并能逆转雷帕霉素对EPCs增殖、迁移和血管形成能力的抑制作用（P<0.05）。结论:雷帕霉素能抑制EPCs增殖和迁移，并呈浓度和时间依赖性。水飞蓟素能增强EPCs增殖和迁移，抑制其凋亡，并呈浓度依赖性。水飞蓟素能抑制雷帕霉素对EPCs的促凋亡作用，并能逆转雷帕霉素对EPCs增殖、迁移和血管形成能力的抑制作用。
Abstract:
AIM:To study the effect of rapamycin on proliferation and migration of endothelial progenitor cells (EPCs) and to observe the protective effect of silymarin on EPCs under rapamycin intervention. METHODS: Peripheral blood was collected from human volunteers. Mononuclear cells (MNCs) were separated by density centrifugation and were induced to differentiate into EPCs in vitro. EPCs were intervened with different concentrations of rapamycin (0, 0.1, 1, 10, 100 ng/ml) for 24 h and different times (0, 6, 12, 24, 48 h) and proliferation and migration of EPCs were then detected. EPCs were intervened with different concentrations of silymarin (0, 25, 50, 100 μg/ml) for 24 h and proliferation, migration and apoptosis of EPCs were then detected. Rapamycin (1 ng/ml) and silymarin (25, 50, 100 μg/ml) were added in EPCs for 24 h and proliferation, migration, apoptosis and angiogenesis were then detected. RESULTS: Compared with those in the control group, rapamycin (1, 10, 100 ng/ml) inhibited proliferation and migration of EPCs in a concentration and timedependent manner (P<005). Silymarin (50, 100 μg/ml) enhanced proliferation and migration of EPCs and inhibition of apoptosis in a concentrationdependent manner (P<005). After adding rapamycin (1 ng/ml) and silymarin (25, 50, 100 μg/ml) for 24 h, silymarin inhibited the proapoptotic effect of rapamycin on EPCs and reversed the inhibitive effect of rapamycin on proliferation, migration and angiogenesis of EPCs (P<005). CONCLUSION: Rapamycin inhibits proliferation and migration of EPCs in a concentration and timedependent manner. Silymarin enhances proliferation and migration of EPCs and inhibition of apoptosis in a concentrationdependent manner. Silymarin also inhibits the proapoptotic effect of rapamycin on EPCs and reverses the inhibitive effect of rapamycin on proliferation, migration and angiogenesis of EPCs.

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备注/Memo

备注/Memo:
收稿日期：2013-01-04.基金项目：上海市科学技术委员会科研计划项目资助(10411963900) 通讯作者：任雨笙，主任医师，主要从事冠心病临床及基础研究 Email:renyusheng@gmail.com 作者简介：张鹏，主治医师 Email:zhangpeng1996@gmail.com
更新日期/Last Update: 2013-07-29