[1]刘宏,柳青,雷寒,等.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[J].第三军医大学学报,2010,32(16):1728-1731.
 Liu Hong,Liu Qing,Lei Han,et al.Inflammatory stress promotes lipid accumulation in aorta of scavenger double knockout mice[J].J Third Mil Med Univ,2010,32(16):1728-1731.
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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(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
32卷
期数:
2010年第16期
页码:
1728-1731
栏目:
论著
出版日期:
2010-08-30

文章信息/Info

Title:
Inflammatory stress promotes lipid accumulation in aorta of scavenger double knockout mice
作者:
刘宏柳青雷寒李秀兰陈显
重庆医科大学附属第一医院:临床研究中心,心血管内科
Author(s):
Liu Hong Liu Qing Lei Han Li Xiulan Chen Xian
Department of Clinical Research Center,Department of Cardiology, First Affiliated Hospital, Chongqing Medical University, Chongqing, 400016, China
关键词:
炎症清道夫受体ACD36基因敲除固醇调节元件结合蛋白
Keywords:
inflammatory stress scavenger receptor A CD36 gene knock out sterol regulatory element binding protein
分类号:
R543.502;R364.5;R394.1
文献标志码:
A
摘要:
目的    探讨炎症促进清道夫受体A和CD36双敲(SR double knockout, SR DKO) C57BL/6J小鼠主动脉固醇调节元件结合蛋白2(sterol regulatory element binding protein2, SREBP2)表达,加重主动脉脂质异常积聚的分子机制。    方法    13只SR DKO雄性小鼠,按体质量大小,采用完全随机的方法,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,P<0.05];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明显增高(P<0.05)。    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。
Abstract:

Objective To investigate whether inflammatory stress exacerbates lipid accumulation and the mechanism of up - regulation of sterol regulatory element binding protein 2 (SREBP2) expression in the aorta of scavenger receptor double knockout (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 10% (w/v) 0 . 5 ml casein injection ( n =6). After 14 weeks, the mice were sacrificed, and the blood sample of right atrium was collected and the aorta was taken. Inflammatory cytokines, such as serum amyloid A (SAA), IL - 6 and TNF - α was determined by ELISA. Serum levels of total cholesterol (TC) and low - density lipid cholesterol (LDL - C) were detected by enzymatic assay. Frozen sections of aorta were stained with Red Oil O to visualize lipid accumulation. Both the mRNA and protein expressions of SREBP2, SREBP cleavage - activating protein (SCAP) and low density lipoprotein receptor (LDLr) in the aorta were measured by real - time polymerase chain reaction and immunohistochemical staining respectively.  Results Increased of serum SAA was observed in inflammatory mice (10.32 ± 2.88 vs 5.50 ± 2.67 ng/ml, P <0 . 05). In the inflammatory mice, a increase in SREBP2, SCAP and LDLr mRNA level of the aorta, as well as mature SREBP2, SCAP and LDLr proteins abundance were found, when compared with control animals ( P <0 . 05).  Conclusion Inflammatory SR DKO mice are associated with increased SREBP2 gene expression of aortas. This is probably the cause for enhanced SCAP gene expression and, consequently, for increase cholesterol uptake through LDLr pathway and for promoting lipid accumulation in aortas of the mice with absence of uptake of modified LDL.

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更新日期/Last Update: 2010-08-31