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血管紧张素Ⅱ在正常和高血压条件下上调心肌细胞中基质金属酶蛋白-2和组织金属酶蛋白抑制物-1的表达

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第5期
页码:
508-513,519
栏目:
基础研究
出版日期:
2014-05-25

文章信息/Info

Title:
Angiotensin II upregulates expressions of matrix metaIloproteinase-2 and tissue inhibitors of metalloproteinase-1 in cardiomyocytes
作者:
拓步雄; 李超民; 彭利静; 刘 薇; 李 慧
(解放军第四五一医院心血管内科,陕西 西安 710054)
Author(s):
TUO Bu-xiong;  LI Chao-min;  PENG Li-jing;  LIU Wei;  LI Hui
(Department of Cardiology, PLA 451 Hospital, Xi’an 710054, Shaanxi, China)
关键词:
原发性高血压; 血管紧张素Ⅱ; 基质金属酶蛋白-2; 组织金属酶蛋白抑制物-1
Keywords:
essential hypertension;  angiotensin II;  matrix metaIloproteinase-2;  tissue inhibitors of metalloproteinase-1
分类号:
R541.3
DOI:
-
文献标识码:
A
摘要:
目的:研究在正常和高血压条件下血管紧张素Ⅱ（AngⅡ）对心肌细胞中基质金属酶蛋白-2（MMP-2）和组织金属酶蛋白抑制物-1（TIMP-1）表达的影响，观察其对氧化应激的影响。方法： AngⅡ预处理体外培养的原代心肌细胞，利用试剂盒检测细胞中丙二醛水平、谷胱甘肽过氧化物酶（GPx）和超氧化物歧化酶（SOD）活力的变化；同时利用实时定量PCR （qRT-PCR）和蛋白免疫印迹（Western blot）方法检测细胞中MMP-2和TIMP-1基因信使核糖核苷酸（mRNA）和蛋白的表达变化。建立大鼠高血压模型，检测模型大鼠及缬沙坦治疗大鼠心肌组织中丙二醛、GPx和SOD酶活力的变化，并运用qRT-PCR和Western blot方法分析心肌组织中MMP-2和TIMP-1基因mRNA和蛋白的表达变化。 结果： AngⅡ预处理能显著提高心肌细胞中氧化应激水平，同时AngⅡ预处理上调心肌细胞中MMP-2和TIMP-1基因表达。在高血压大鼠中，心肌组织的氧化应激水平明显高于假手术组，而经AngⅡ受体阻断剂缬沙坦处理后氧化应激水平则下降。并且，缬沙坦治疗也能降低高血压大鼠心肌组织中MMP-2和TIMP-1基因表达。 结论： AngⅡ可同时上调氧化应激并调控MMP-2基因和TIMP-1基因在心肌细胞中的表达，但其具体机制还不完全清楚，仍需进一步探讨。
Abstract:
AIM:To investigate the effect of angiotensin II (AngII) on the expressions of matrix metalloproteinase-2 (MMP-2) and tissue inhibitors of metalloproteinase-1 (TIMP-1). METHODS: Cultured cardiomycytes were pretreated with AngII. The level of malonaldehyde (MDA) and enzyme activity of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were detected by commercial kits. The mRNA and protein expressions of MMP-2 and TIMP-1 in cardiomyocytes were analyzed by qRT-PCR and Western blot. The rat hypertension model was established and the levels of MDA in the heart tissue of model rats and valsartan-treated rats were detected along with the enzyme activity of GPx and SOD. Expressions of MMP-2 and TIMP-1 were also analyzed by qRT-PCR and Western blot. RESULTS: Pretreatment with AngII significantly increased the oxidative stress in myocardial cells and also induced the upregulation of the expressions of MMP-2 and TIMP-1. In hypertensive rats, the oxidative stress in myocardial tissue was significantly higher than that in sham group, but the stress decreased after valsartan treatment. Valsartan also reduced the expressions of MMP-2 and TIMP-1 gene in myocardial tissue of hypertensive rats. CONCLUSION: Oxidative stress increase via AngII is involved in the regulation of MMP-2 and TIMP-1 expression. The mechanism deserves further research.

参考文献/References

[1]Lifton RP,Gharavi AG,Geller DS.Molecular mechanisms of human hypertension[J].Cell,2001,104(4):545-556.
[2]Young MJ,Rickard AJ.Mechanisms of mineralocorticoid salt-induced hypertension and cardiac fibrosis[J].Mol Cell Endocrinol,2012,350(2):248-255.
[3]Hubmacher D,Apte SS.The biology of the extracellular matrix:novel insights[J].Curr Opin Rheumatol,2013,25(1):65-70.
[4]Kandasamy AD,Chow AK,Ali MA,et al.Matrix metalloproteinase-2 and myocardial oxidative stress injury:beyond the matrix[J].Cardiovasc Res,2010,85(3):413-423.
[5]Lacchini R,Jacob-Ferreira AL,Luizon MR,et al.Common matrix metalloproteinase 2 gene haplotypes May modulate left ventricular remodelling in hypertensive patients[J].J Hum Hypertens,2012,26(3):171-177.
[6]Caruso R,Caselli C,Boroni C,et al.Relationship between myocardial redox state and matrix metalloproteinase activity in patients on left ventricular assist device support[J].Circ J,2011,75(10):2387-2396.
[7]Wang X,Chow FL,Oka T,et al.Matrix metalloproteinase-7 and ADAM-12(a disintegrin and metalloproteinase-12)define a signaling axis in agonist-induced hypertension and cardiac hypertrophy[J].Circulation,2009,119(18):2480-2489.
[8]Wang X,Oka T,Chow FL,et al.Tumor necrosis factor-alpha-converting enzyme is a key regulator of agonist-induced cardiac hypertrophy and fibrosis[J].Hypertension,2009,54(3):575-582.
[9]Baker AH,Edwards DR,Murphy G.Metalloproteinase inhibitors: biological actions and therapeutic opportunities[J].J Cell Sci,2002,115(Pt 19):3719-3727.
[10]Ahmed SH,Clark LL,Pennington WR,et al.Matrix metalloproteinases/tissue inhibitors of metalloproteinases:relationship between changes in proteolytic determinants of matrix composition and structural, functional, and clinical manifestations of hypertensive heart disease[J].Circulation,2006,113(17):2089-2096.
[11]Lindsay MM,Maxwell P,Dunn FG.TIMP-1:a marker of left ventricular diastolic dysfunction and fibrosis in hypertension[J].Hypertension,2002,40(2):136-141.
[12]Siwik DA,Pagano PJ,Colucci WS.Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts[J].Am J Physiol Cell Physiol,2001,280(1):C53-C60.
[13]Brew K,Nagase H.The tissue inhibitors of metalloproteinases (TIMPs): an ancient family with structural and functional diversity[J].Biochim Biophys Acta,2010,1803(1):55-71.
[14]Hitomi H,Kiyomoto H,Nishiyama A.Angiotensin II and oxidative stress[J].Curr Opin Cardiol,2007,22(4):311-315.
[15]Nishiyama A,Yoshizumi M,Rahman M,et al.Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats[J].Kidney Int,2004,65(3):972-981.
[16]Zhang GX,Kimura S,Nishiyama A,et al.ROS during the acute phase of Ang II hypertension participates in cardiovascular MAPK activation but not vasoconstriction[J].Hypertension,2004,43(1):117-124.
[17]Galli A,Svegliati-Baroni G,Ceni E,et al.Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism[J].Hepatology,2005,41(5):1074-1084.
[18]Kelly PJ,Morrow JD,Ning M,et al.Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke: the Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke)study[J].Stroke,2008,39(1):100-104.
[19]Spinale FG.Matrix metalloproteinases: regulation and dysregulation in the failing heart[J].Circ Res,2002,90(5):520-530.
[20]高修仁,彭龙云,麦炜颐,等.高血压大鼠心肌中MMP-2的蛋白表达及其RAS阻断后的变化[J].中山大学学报(医学科学版),2003,24(1):30-34.

备注/Memo

备注/Memo:
收稿日期：2014-03-25.
通讯作者：李慧，副主任医师，主要从事冠心病、高血压病诊治研究 Email:Lit-mouse@163.com
作者简介：拓步雄，主任医师 Email:swatt@126.com
更新日期/Last Update: 2014-06-05