ox-LDL通过NAD依赖性脱乙酰酶SIRT1抑制MHC Ⅱ反式激活蛋白的转录活性  

Ox-LDL inhibits the transcriptional activity of trans-activating pratein MHC Ⅱ by NAD dependent of the deacetylase SIRT1

作　　者：方明明[1] 宋鸣子[1] 周红[2] 吴晓燕[2] 

机构地区：[1]江苏建康职业学院医学系,江苏南京210029 [2]南京医科大学基础医学国家级实验教学示范中心,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2014年第4期405-409,共5页Journal of Nanjing Medical University(Natural Sciences)

基　　金：国家自然科学基金青年资助(31200645);南京医科大学科技发展基金项目(2011NJMU268)

摘　　要：目的：探讨氧化低密度脂蛋白（ox-LDL）对NAD依赖性脱乙酰酶（NAD-dependent deacetylase）SIRT1表达的影响,及SIRT1调节人体适应性免疫应答过程中的机制。方法：体外培养人的原代外周血单核细胞,经集落刺激因子（GM-CSF）刺激分化7 d形成巨噬细胞,将分化良好的巨噬细胞分别用不同浓度ox-LDL（0-120μg/ml）培养48 h。应用Western blot方法检测细胞内SIRT1的蛋白表达变化,Real-time PCR检测SIRT1、HLA-DRα的mRNA水平。结果：SIRT1蛋白表达随ox-LDL浓度的升高而降低;ox-LDL处理后,SIRT1的mRNA水平与对照组比较显著降低（P〈0.05）;SIRT1激动剂白藜芦醇能够逆转ox-LDL诱导的HLA-DRα启动子的活性下调。结论：ox-LDL通过调节巨噬细胞中SIRT1的蛋白表达和mRNA水平,使依赖MHCⅡ反式激活蛋白（class II trans-activator,CIITA）的HLA-DRα启动子活性下降,提示脱乙酰酶SIRT1可能是临床上干预动脉粥样硬化的潜在靶位点。Objective：To investigate the effects of oxidized low-density lipoprotein（ox-LDL） on the expression and activity of NAD- dependent deacetylase SIRT1 and its regulatory mechanisms on human adaptive immune function. Methods：Human primary peripheral blood monoeytes were induced by human macrophage colony stimulating factor GM-CSF for 7 days in vitro. Well differentiated macrophages were treated with different concentrations （0-120 μg/ml） of ox-LDL for 48 h. The protein expression of SIRT1 was detected by Western blot. Real-time PCR was performed to examine the SIRT1 and HLA-DRα mRNA. Results：The protein expression of SIRT1 was decreased by ox-LDL in a concentration-dependent manner. The mRNA of SIRT1 treated by ox-LDL was significantly lower than that of the control group （P 〈 0.05）.Resveratrol,whieh is the agonist of SIRT1 ,rescued the decreased expression of HLA-DRα induced by ox-LDL. Conclusion：The CIITA-dependent HLA-DRα promoter activity was decreased when treated with ox-LDL,which was induced by the change of mRNA and protein expression of SIRT1 in macrophage. Therefore, deaeetylase SIRT1 may provide potential target for the treatment of atherosclerosis.

关 键 词：氧化低密度脂蛋白 SIRT1 动脉粥样硬化 CIITA 

分 类 号：R543.5[医药卫生—心血管疾病]