炎症促进清道夫受体基因敲除小鼠主动脉脂质积聚的分子机制刘宏1.DOC

炎症促进清道夫受体基因敲除小鼠主动脉脂质积聚的分子机制 刘 宏[基金项目] 国家自然科学基金面上项目[通信作者] 柳 青, E-mail:qingliu5566@yahoo.cn1，柳 青1，雷 寒2，李秀兰1，陈 显1 （400016 重庆，重庆医科大学附属第一医院： 临床研究中心1 [基金项目] 国家自然科学基金面上项目 [通信作者] 柳 青, E-mail:qingliu5566@yahoo.cn [摘要] 目的 探讨炎症促进清道夫受体A和CD36双敲（SR DKO）C57BL/6J小鼠主动脉固醇调节元件结合蛋白2（SREBP2）表达，加重主动脉脂质异常积聚的分子机制。方法 SR DKO雄性小鼠，随机分为炎症组（n=6）和对照组(n=7)。喂养高脂饮食14周，检测血清炎症因子和脂质水平；油红O染色观察主动脉脂质积聚；实时定量PCR和免疫组织化学染色，分析主动脉低密度脂蛋白受体（LDLr）、调控其转录的SREBP2及SREBP2裂解激活蛋白（SCAP）mRNA和蛋白表达水平。结果 炎症组血清淀粉样蛋白A(SAA)水平比对照组明显增高[（10.32±2.88）ng/ml vs （5.50±2.67） ng/ml，差异有统计学意义( P0.05)]；炎症组血清总胆固醇（TC）和LDL水平显著低于对照组[（1.68±0.17）mmol/L vs （2.34±0.42）mmol/L；(1.00±0.16) mmol/L vs (1.35±0.26) mmol/L，差异均有统计学意义( P0.05)]；主动脉切片油红O染色结果发现，炎症组比对照组脂质积聚明显增加；炎症组主动脉的SREBP2、SCAP和LDLr mRNA和蛋白表达水平比对照组增高。结论 SR DKO小鼠在炎症状态下，促进主动脉胆固醇敏感器SCAP和SREBP2表达，上调LDLr，使胞内摄入胆固醇增加，加重主动脉脂质的异常积聚。 [关键词] 炎症；清道夫受体A；CD36；基因敲除；固醇调节元件结合蛋白 [中图法分类号] [文献标志码] A Inflammatory stress promotes Lipid Accumulation in aorta of scavenger double knockout mice LIU Hong1,LIU Qing1,LEI Han2,LI Xiulan1,CHEN Xian1 ( 1 Department of Clinical Research Center, 2 Department of Cardiology, The First Affiliated Hospital, Chongqing Medical University, Chongqing 400016,China)] [Abstract] Objective To investigate whether in?ammatory stress exacerbates lipid accumulation and the mechanism of up-regulation of sterol regulatory element binding protein 2 (SREBP2) expression in aorta of scavenger receptor double knock-out (SR DKO) mice. Methods Male SR DKO mice fed with high lipid diet were randomly divided into the control group (n=7) and the inflammation group induced by casein injection (n=6) . After 14 weeks, inflammatory cytokines was determined by ELISA．Serum levels of total cholesterol (TC) and LDL-C were detected by enzymatic assay. Frozen sections of aorta were stained with Red Oil O to be visualized lipid accumulation. Both the gene and protein expressions of SREBP2, SREBP cleavage-activating protein (SCAP)