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0.001,0.01,0.1,1.0μmol/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48h,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0.01,0.1,1.0μmol/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0.1μmol/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0.01,0.1,1.0μmol/L组细胞凋亡率下降(P<0.01),其中0.1μmol/L组凋亡率下降最显著(P<0.01)。0.1μmol/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。
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（P 0.01） . Meanwhile,flow cytometry showed apoptosis rate was decreased in simvastatin at concentration of 0.01,0.1,1.0 μmol/L group（P 0.01） ,especially in 0.1 μmol/L group（P 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.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2011年第23期4207-4210,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
