Ⅰ型去乙酰化酶抑制剂MS-275对间充质干细胞C3H/10T1/2成脂分化的影响  

Class Ⅰ histone deacetylase inhibitor MS-275 inhibits adipogenic differentiation in mesenchymal stem cells C3H/10T1/2

作　　者：李智耀[1] 王奎栋[1] 吴伟[1] 龚雨琴[1] 季煜华[1] 

机构地区：[1]暨南大学生命科学技术学院组织移植与免疫研究中心,广州510632

出　　处：《第三军医大学学报》2012年第5期415-418,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金(30600587;30900563;81071483);中央高校基础研究资金;江苏省高教厅自然科学资金(10KJB180006)~~

摘　　要：目的探讨Ⅰ型去乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)MS-275对间充质干细胞(mesen-chymal stem cells,MSCs)成脂分化的影响。方法利用噻唑蓝(MTT)和碘化乙啶(PI)染色结合流式细胞术(FCM)分别检测不同浓度MS-275对C3H/10T1/2细胞活性和细胞周期的影响;油红O染色分析MS-275对C3H/10T1/2细胞成脂分化能力的影响;同时应用实时定量PCR(real-time PCR)检测MS-275对成脂分化标志物:脂结合蛋白(aP2)、围脂素(perilipin)、脂联素(Adipoq),以及成脂分化关键转录因子:过氧化物酶体增殖物激活受体-γ2(PPAR-γ2)mRNA转录水平的影响。结果随着MS-275浓度升高,其对C3H/10T1/2细胞的抑制率也随着增高,IC50约为8μmol/L(P<0.05);流式结果表明,MS-275将C3H/10T1/2细胞周期阻滞在G0/G1期;0.5μmol/L的MS-275明显减少C3H/10T1/2细胞的脂滴积累;同时成脂分化标志物aP2、perilipin、Adipoq及成脂关键转录因子PPAR-γ2的转录水平也显著降低(P<0.05)。结论 MS-275减弱了间充质干细胞成脂分化的能力,表明抑制Ⅰ型HDACs的活性可部分抑制MSCs向成脂分化。Objective To investigate the effect of MS-275,a class Ⅰ histone deacetylase inhibitor,on the adipogenic differentiation of mesenchymal stem cells C3H/10T1/2.Methods MTT assay and FCM analysis was used to detect the effect of MS-275 on cell viability and cell cycle of C3H/10T1/2 cells.The effect of MS-275 on the adipogenic capacity of C3H/10T1/2 cells were determined by Oil red O staining.Real-time quantitative polymerase chain reaction（real-time PCR） was employed to detect the mRNA transcription levels of adipogenic differentiation markers,including fat binding protein（aP2）,perilipin,adiponectin（Adipoq） and adipogenic differentiation key transcription factor peroxisome proliferators-actiated receptor-gamma 2（PPAR-γ2） after MS-275 treatment.Results MS-275 inhibited the viability of C3H/10T1/2 cells in a dose-dependent manner,and the IC50 was identified nearly to 8 μmol/L（P0.05）.FCM analysis showed that the cell cycle of C3H/10T1/2 was arrested at G0/G1 phase after MS-275 treatment.Oil red O staining showed that 0.5 μmol/L MS-275 significantly reduced lipid drops accumulation in C3H/10T1/2 cells,and the mRNA transcription levels of aP2,perilipin,Adipoq and adipogenic differentiation key transcription factor PPAR-γ2 were decreased correspondingly（P0.05）.Conclusion MS-275 attenuates the adipogenic differentiation capacity of mesenchymal stem cells,suggesting that inhibiting the activity of classⅠHDACs may partially suppress mesenchymal stem cells into adipogenesis.

关 键 词：间充质干细胞 成脂分化 MS-275 组蛋白去乙酰化酶 

分 类 号：R329-33[医药卫生—人体解剖和组织胚胎学] R329.24[医药卫生—基础医学]