辛伐他汀抑制机械牵张力和氧化低密度脂蛋白所致血管平滑肌细胞全基因组甲基化水平的降低  

Simvastatin inhibits genome-wide methylation in mouse vascular smooth muscle cells induced by stretch stress and oxidized low density lipoprotein

作　　者：刘科峰[1,2] 裴婷[2] 刘树迎[2] 李子卿[3] 平苏宁 王晶晶[2] 汪泓[2] 盛璞义[3] 李朝红[2] Liu Kefeng;Pei Ting;Liu Shuying;Li Ziqing;Ping Suning;Wang Jingjing;Wang Hong;Sheng Puyi;Li Chaohong(Department of Histology and Embryology, Xiangnan University, Chenzhou 423000, China;Department of Histology and Embryology, Zhongshan School of Medicine,Sun Yat-sen University, Guangzhou 510080, China;Departments of orthopedic Surgery,Sun Yat-sen University First Affiliated Hospital, Guangzhou 510080,China)

机构地区：[1]湘南学院组织胚胎学教研室,郴州423000 [2]中山大学中山医学院人体解剖与组织胚胎学教研室,广州510080 [3]中山大学附属第一医院骨外科教研室,广州510080

出　　处：《中国组织化学与细胞化学杂志》2017年第4期360-365,共6页Chinese Journal of Histochemistry and Cytochemistry

基　　金：国家自然科学基金项目(81070124;81500337);广东省科技计划项目(2014A020212109);湖南省教育厅资助科研项目(12C0893);湖南省重点建设学科资金资助(湘教发[2011]76号)

摘　　要：目的探讨小鼠血管平滑肌细胞(vascular smooth muscle cells,VSMCs)在机械牵张力(stretch stress,SS)和氧化低密度脂蛋白(oxidized low-density lipoprotein,ox LDL)作用下全基因组甲基化水平的变化,并进一步考察辛伐他汀(simvastatin,SIM)对此变化的影响。方法血浆制备氧化型低密度脂蛋白,体外常规培养VSMCs,施加机械牵张力和/或氧化型低密度脂蛋白,或用辛伐他汀预处理1h后再施加刺激,用荧光探针5-甲基胞嘧啶检测VSMCs全基因组甲基化水平。以细胞免疫荧光定量阳性率和SPSS统计软件对甲基化水平进行分析。结果机械牵张力和氧化型低密度脂蛋白均可降低VSMCs的全基因组甲基化水平,且两者联合作用大于单一因素,辛伐他汀预处理VSMCs可部分抑制机械牵张力和/或氧化低密度脂蛋白诱导的全基因组甲基化水平降低。结论机械牵张力和氧化低密度脂蛋白可分别促进VSMCs全基因组甲基化水平降低,当两者共处理时呈相加作用,辛伐他汀可部分抑制上述效应。Objective To investigate genome-wide methylation in mouse vascular smooth muscle cells(VSMCs)induced bystretch stress(SS)and oxidized low-density lipoprotein(oxLDL),and the role of simvastatin in this process.Methods VSMCs weretreated with SS and/or oxLDL prepared from plasma with or without pre-incubation of simvastatin for60min.The methylation wasdetected using5-methylcytosine fluorescent probe.The level of methylation was determined by fluorescence positive rate which wasquantified using SPSS analysis.Results Either SS or ox-LDL decreased the genome-wide methylation of VSMCs.The combination ofboth caused more significant reduction.Simvastatin partly inhibited the effect induced by SS and/or oxLDL.Conclusion Both SS andox-LDL can reduce genome-wide methylation in VSMCs independently,and to a higher degree when applied together.Simvastatincan partly abolish this effect.

关 键 词：辛伐他汀 机械牵张力 氧化低密度脂蛋白 全基因组甲基化 血管平滑肌细胞 动脉粥样硬化 

分 类 号：R34[医药卫生—基础医学]