我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

孤儿核受体Nur77参与AopE-/-小鼠颈动脉易损斑块的形成

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第4期
页码:
373-377,383
栏目:
基础研究
出版日期:
2014-04-25

文章信息/Info

Title:
Orphan receptor Nur77 participates in formation of vulnerable carotid atherosclerotic plaque in ApoE-/- mice
作者:
蔡招华; 聂 鹏; 于 瀛; 崔明丽; 孙士群; 沈玲红; 何 奔
(上海交通大学医学院附属仁济医院心内科，上海 200127)
Author(s):
CAI Zhao-hua;  NIE Peng;  YU Ying;  CUI Ming-li;  SUN Shi-qun;  Shen Ling-hong;  HE Ben
(Department of Cardiology, Renji Hospital, Medical College, Shanghai Jiaotong University, Shanghai 200025, China)
关键词:
动脉粥样硬化; 易损斑块; 巨噬细胞; 核受体; Nur77; 小鼠
Keywords:
atherosclerosis;  vulnerable plaque;  macrophage;  nuclear receptor;  Nur77;  mouse
分类号:
R543.4;Q463
DOI:
-
文献标识码:
A
摘要:
目的:研究孤儿核受体Nur77在AopE-/-小鼠动脉粥样硬化易损斑块形成中的作用。方法： AopE-/-小鼠左肾动脉和左颈总动脉联合部分结扎建立颈动脉易损斑块模型，采用HE染色观察斑块病理学改变，免疫荧光染色结合激光扫描共聚焦显微镜技术观察斑块中Nur77蛋白的表达。同时，体外培养小鼠巨噬细胞系RAW264.7，在氧化低密度脂蛋白（oxLDL）及其主要成分7-酮胆固醇（7-ketocholesterol，7-KC）或者游离胆固醇（FC），以及炎症介质（LPS、IL-1β）等条件刺激下，应用蛋白免疫印迹技术（Western blot）检测Nur77蛋白表达变化。结果： AopE-/-小鼠颈动脉易损斑块局部有Nur77蛋白高表达，而oxLDL及其组成成分（7-KC和FC）以及某些炎症介质（如LPS、IL-1β等）均能在RAW264.7细胞中诱导Nur77蛋白表达上调。结论： 孤儿核受体Nur77可能在动脉粥样硬化易损斑块发展进程中发挥着重要作用。
Abstract:
AIM:To investigate whether orphan receptor Nur77 is involved in the formation of vulnerable carotid atherosclerotic plaque in ApoE-/- mice. METHODS: Using the method of partial ligation of left carotid and left renal arteries, we generated an ApoE-/- mouse model of vulnerable carotid atherosclerotic plaque. The pathological changes of atherosclerotic plaques were observed using H/E staining and the expression of Nur77 was detected by laser confocal microscopy after immunofluorescence staining. Macrophages (murine RAW 264.7 cells) were cultured and were stimulated with oxLDL and its main lipid components 7-ketocholesterol (7-KC) or free cholesterol (FC) and some inflammatory mediators (LPS or IL-1β). The protein expression of Nur77 was detected by Western blotting. RESULTS: Nur77 is highly expressed in vulnerable carotid atherosclerotic plaques in ApoE-/- mice. In addition, oxLDL and its main lipid components (7-KC or FC) and some inflammatory mediators (LPS or IL-1β) induced the expression of Nur77 in murine RAW 264.7 cells in vitro. CONCLUSION: Orphan receptor Nur77 participates in the formation of vulnerable carotid atherosclerotic plaque in ApoE-/- mice.

参考文献/References

[1]Martinez-Gonzalez J,Badimon L.The NR4A subfamily of nuclear receptors:new early genes regulated by growth factors in vascular cells[J].Cardiovasc Res,2005,65(3):609-618.
[2]Pols TW,Bonta PI,de Vries CJ.NR4A nuclear orphan receptors:protective in vascular disease?[J].Curr Opin Lipidol,2007,18(5):515-520.
[3]Maxwell MA,Muscat GE.The NR4A subgroup:immediate early response genes with pleiotropic physiological roles[J].Nucl Recept Signal,2006,4:e002.
[4]Arkenbout EK,de Waard V,van Bragt M,et al.Protective function of transcription factor TR3 orphan receptor in atherogenesis:decreased lesion formation in carotid artery ligation model in TR3 transgenic mice[J].Circulation,2002,106(12):1530-1535.
[5]Bonta PI,Matlung HL,Vos M,et al.Nuclear receptor Nur77 inhibits vascular outward remodelling and reduces macrophage accumulation and matrix metalloproteinase levels[J].Cardiovasc Res,2010,87(3):561-568.
[6]Wang RH,He JP,Su ML,et al.The orphan receptor TR3 participates in angiotensin II-induced cardiac hypertrophy by controlling mTOR signaling[J].EMBO Mol Med,2013,5(1):137-148.
[7]Cheng Z,V?lkers M, Din S,et al.Mitochondrial translocation of Nur77 mediates cardiomyocyte apoptosis[J].Eur Heart J,2011,32(17):2179-2188.
[8]De Vries CJ,van Achterberg TA,Horrevoets AJ,et al.Differential display identification of 40 genes with altered expression in activated human smooth muscle cells.Local expression in atherosclerotic lesions of smags, smooth muscle activation-specific genes[J].J Biol Chem,2000,275(31):23939-23947.
[9]Pei LM,Castrillo A,Tontonoz P.Regulation of Macrophage Inflammatory Gene Expression by the Orphan Nuclear Receptor Nur77[J].Mol Endocrinol,2006,20(4):786-794.
[10]Bonta PI,van Tiel CM,Vos M,et al.Nuclear receptors Nur77,Nurr1,and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses[J].Arterioscler Thromb Vasc Biol,2006,26(10):2288-2294.
[11]Jin SX,Shen LH,Nie P,et al.Endogenous renovascular hypertension combined with low shear stress induces plaque rupture in apolipoprotein E-deficient mice[J].Arterioscler Thromb Vasc Biol,2012,32(10):2372-2379.
[12]Katagiri Y,Takeda K,Yu ZX,et al.Modulation of retinoid signalling through NGF-induced nuclear export of NGFI-B[J].Nat Cell Biol,2000,2(7):435-440.
[13]Okabe T,Takayanagi R,Adachi M,et al.Nur77, a member of the steroid receptor superfamily,antagonizes negative feedback of ACTH synthesis and secretion by glucocorticoid in pituitary corticotrope cells[J].J Endicriol,1998,156(1):169-175.
[14]Sekiya T,Kashiwagi I,Yoshida R,et al.Nr4a receptors are essential for thymic regulatory T cell development and immune homeostasis[J].Nat Immunol,2013, 4(3):230-237.
[15]Li H,Kolluri SK,Gu J,et al.Cytochrome C release and apoptosis induced by mitochondrial targeting of nuclear receptor TR3[J].Science,2000,289(5482):1159-1164.
[16]Hanna RN,Carlin LM,Hubbeling HG,et al.The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes[J]. Nat Immunol,2011,12(8):778-785.
[17]Yao PM,Tabas I.Free cholesterol loading of macrophages induces apoptosis involving the fas pathway[J].J Biol Chem,2000,275(31):23807-23813.
[18]Thorp E,Li G,Seimon TA,et al. Reduced apoptosis and plaque necrosis in advanced atherosclerotic lesions of Apoe-/- and Ldlr-/- mice lacking CHOP[J].Cell Metab,2009,9(5):474-481.

备注/Memo

备注/Memo:
收稿日期：2014-03-12.基金项目：国家自然科学基金面上项目资助（30971185，81070239）通讯作者：何奔，教授，主要从事冠状动脉粥样硬化基础与临床研究 Email：heben1025@126.com 共同通讯作者：沈玲红，副教授，主要从事冠状动脉粥样硬化基础与临床研究 Email：rjshenlinghong@126.com 作者简介：蔡招华，硕士生 Email：caizhaohua1987@126.com
更新日期/Last Update: 2014-05-06