中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (23): 4207-4210.doi: 10.3969/j.issn.1673-8225.2011.23.007

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

辛伐他汀对高糖高脂诱导人骨髓间充质干细胞凋亡的影响

赵  婕1,李华青2,李  晶1,薛国芳1,陈  彦1,齐  凯3,董  敏3,王惠珍3,牛  勃4   

  1. 1山西医科大学第二医院,山西省太原市   030001
    2山西省晋中市第二医院,山西省晋中市  030008
    3山西医科大学生化教研室,山西省太原市 030001
    4首都儿科研究所生物技术室,北京市  100020
  • 收稿日期:2011-02-09 修回日期:2011-03-12 出版日期:2011-06-04 发布日期:2011-06-04
  • 通讯作者: 牛勃,首都儿科研究所生物技术室,北京市 100020
  • 作者简介:赵婕☆,女, 1968年生,汉族,副主任医师,山西医科大学第二医院在读博士。

Effects of simvastatin on the apoptosis of human mesenchymal stem cells induced by high glucose and saturated fatty acids

Zhao Jie1, Li Hua-qing2, Li Jing1, Xue Guo-fang1, Chen Yan1, Qi Kai3, Dong Min3, Wang Hui-zhen3, Niu Bo4   

  1. 1The Second Hospital of Shanxi Medical University, Taiyuan  030001, Shanxi Province, China
    2The Second Hospital of Jinzhong, Jinzhong  030008, Shanxi Province, China
    3Department of Biochemistry, Shanxi Medical University, Taiyuan  030001, Shanxi Province, China
    4Department of Biotechnology, Capital Institute of Pediatrics, Beijing  100020, China
  • Received:2011-02-09 Revised:2011-03-12 Online:2011-06-04 Published:2011-06-04
  • Contact: Niu Bo, Department of Biotechnology, Capital Institute of Pediatrics, Beijing 100020, China
  • About author:Zhao Jie☆, Studying for doctorate, Associate chief physician, The Second Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi Province, China

摘要:

背景:研究表明,他汀类药物能够促进骨髓间充质干细胞的增殖与黏附能力,抑制高糖高脂培养下骨髓间充质干细胞的凋亡。
目的:观察辛伐他汀对高糖高脂诱导条件下人骨髓间充质干细胞凋亡的影响。
方法:将0.001,0.01,0.1,1.0 μmol/L辛伐他汀分别与高糖高脂诱导条件下人骨髓间充质干细胞培养48 h,以正常培养骨髓间充质干细胞及高糖高脂诱导条件下培养的骨髓间充质干细胞为对照。倒置显微镜下观察细胞形态,MTT法比较不同浓度辛伐他汀对高糖高脂环境下骨髓间充质干细胞存活率的影响,应用流式细胞术检测细胞凋亡,加入PI3K/Akt信号转导通路抑制剂LY294002后辛伐他汀对骨髓间充质干细胞凋亡的影响。
结果与结论:与高糖高脂诱导组比较,辛伐他汀0.01,0.1,1.0 µmol/L组骨髓间充质干细胞存活率均升高(P < 0.01),其中辛伐他汀浓度在0.1 μmol/L时骨髓间充质干细胞存活率升高最显著(P < 0.01);同时流式细胞仪检测结果显示,辛伐他汀0.01,0.1,1.0 µmol/L组细胞凋亡率下降(P< 0.01),其中0.1 µmol/L组凋亡率下降最显著(P < 0.01)。0.1 µmol/L辛伐他汀对骨髓间充质干细胞的影响可被LY294002阻断。说明辛伐他汀能抑制高糖高脂诱导条件下骨髓间充质干细胞的凋亡,其机制可能与PI3K/Akt信号途径有关。

关键词: 辛伐他汀, 骨髓, 间充质干细胞, 凋亡, PI3K/Akt信号途径

Abstract:

BACKGROUND: Previous studies demonstrated that statins can promote the proliferation and adhesion of bone marrow mesenchymal stem cells (BMSCs), inhibit apoptosis of BMSCs cultured with high glucose and saturated fatty acids.
OBJECTIVE: To investigate the effects of simvastatin on the apoptosis of human mesenchymal stem cells induced by high glucose and saturated fatty acids.
METHODS: Different concentrations of simvastatin (0.001, 0.01, 0.1, 1.0 μmol/L) was cultured with BMSCs in presence of high glucose and saturated fatty acids for 48 hours. BMSCs cultured with normal bone marrow mesenchymal stem cells induced by high glucose and saturated fatty acids were as controls. Cell morphology was observed under the inverted microscope. Effect of simvastatin on cell survival rate of BMSCs in high glucose and saturated fatty acids was measured by MTT assay. Cell apoptosis was detected by flow cytometry. LY294002 (PI3K inhibitor) was used to study the underlying mechanism of simvastatin effect on BMSCs apoptosis.
RESULTS AND CONCLUSION: Compared with induced by high glucose and saturated fatty acid group, the survival rate of BMSCs in different concentrations of simvastatin (0.001, 0.01, 0.1, 1.0 μmol/L) group was increased (P < 0.01), especially in simvastatin at concentration of 0.1μmol/L ( < 0.01). Meanwhile, flow cytometry showed apoptosis rate was decreased in simvastatin at concentration of 0.01, 0.1, 1.0 μmol/L group ( < 0.01), especially in 0.1 μmol/L group ( < 0.01). The effect of simvastatin at concentration of 0.1μmol/L on BMSCs could be blocked. The results suggested that simvastatin can inhibit BMSCs apoptosis induced by high glucose and saturated fatty acids, and its mechanism may be related to PI3K/Akt pathway.

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