期刊文献+

阿霉素对心肌基质金属蛋白酶和基质金属蛋白酶组织抑制因子表达的影响

Effect of Adriamycin on the Expressions of MMPs and TIMP- 1 in Myocardium of Rats
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摘要 目的研究阿霉素对大鼠心肌的基质金属蛋白酶(MMPs)和基质金属蛋白酶组织抑制因子(TIMP-1)表达的影响.方法采用RT-PCR测定mRNA水平,采用Westernblotting测定蛋白质水平及蛋白质磷酸化.结果阿霉素处理导致大鼠心肌组织MMP-2、MMP-9、TIMP-1mRNA和蛋白质水平均升高.阿霉素处理还诱导p38MAPK激酶磷酸化水平增加,但不影响Erk1/2和JNKMAPK激酶磷酸化水平.结论在阿霉素介导的心衰发展过程中,胞外基质的降解和累积同时发生.p38MAPK激酶可能参与了阿霉素诱导的心肌毒性作用. Objective To study the effect of adriamycin on the expressions of MMPs and TIMP-1 in myocardium of rats. Methods The mRNA levels of genes were detected by RT-PCR. The protein levels and phosphorylation were determined by Western blotting. Results Adriamycin treatment resulted in an increase in both mRNA and protein levels of MMP-2, MMP-9 and TIMP-1 in myocardium. Adriamycin treatment promoted the phosporylation of p38 MAPK, rather than Erkl/2 and JNK MAPKs. Conclusion The degradation and accumulation of extracellular matrix probably occurred simultantly, p38 MAPK is involved in adriamycin-induced cardiotoxicity.
出处 《昆明医学院学报》 2009年第2期5-8,共4页 Journal of Kunming Medical College
基金 国家自然科学基金资助项目(30560036)
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参考文献12

  • 1RABELO E, D E ANGELIS K, BOCK P, et al. Baroreflex sensitivity and oxidative stress in adriamycin-induced heart failure[ J ]. Hypertension, 2001,38 : 576 - 580.
  • 2李世红,王绍军.阿霉素心脏毒性发病机制新近展[J].临床心血管病杂志,2005,21(4):249-252. 被引量:19
  • 3WOESNER J F. Matrix metalloproteinases and their inhibitors in connective tissue remodeling [J]. FASEB J, 1991,5:2145 - 2154.
  • 4ROTEN L, NEMOTO S, SIMSIC J, et al. Effects of gene deletion of the tissue inhibitor of the matrix metalloproteinase type 1 (TIMP-1) on left ventricular geometry and function in mice [J]. J Mol Cell Cardiol, 2000,32:109 - 120.
  • 5COHEN M, MEISSER A,HAENGGELI L,et al. Involvement of MAPK pathway in TNF--induced MMP-9 expression in human trophoblastic cells [J]. Mol Hum Reprod, 2006, 12 : 225 - 232.
  • 6SAKATA Y,YAMAMOTO K,MANO T,et al. Activation of mat rix metalloproteinases precedes left vent rieular remodeling in hypertensive heart failure rats [J]. Circulation, 2004,109 : 2143 - 2149.
  • 7刘洪智,戚本玲,曹林生,曾秋棠,成蓓,管思明,刘承云.基质金属蛋白酶在阿霉素心肌病左室重构中的表达与意义[J].临床心血管病杂志,2005,21(1):26-29. 被引量:6
  • 8YOSHIJI H, KURIYAMA S, YOSHII J, et al. Tissue in - hibitor of metalloproteinases-I attenuates spontaneous liver fibrosis resolution in the transgenic mouse [J]. Hepatology, 2002,36 : 850 - 860.
  • 9SHIOJI K,KISHIMOTO C, NAKAMURA H,et al. Overexpression of thioredoxin-1 in transgenic mice attenuates adriamycin-induced cardiotoxicity [J]. Circulation, 2002,106:1403 - 1409.
  • 10BALACHANDAR A V, MALARKODI K P, VARALAK - SHMI P. Protective role of DLa-lipoic acid against adriamycin-induced cardiac lipid peroxidation [J ]. Hum Exp Toxicol, 2003,22 : 249 - 254.

二级参考文献38

  • 1Thomas C V, Coker M L, Zellner J L, et al. Increased matrix metalloproteinase activity and selective upregulation in LV myocardium from patients with end-stage dilated cardiomyopathy. Circulation, 1998, 97: 1708 -1715.
  • 2Schwarz E R, Pollick C, Dow J, et al. A small animal model of non-ischemic cardiomyopathy and its evaluation by transthoracic echocardiography. Cardiovascular Res, 1998,39: 216-223.
  • 3Brower G L,Janicki J S. Contribution of ventricular remodeling to pathogenesis of heart failure in rats. Am J Physiol Heart Circ Physiol, 2001,280: H674-H683.
  • 4Jayasankar V, Woo Y J, Bish L T, et al. Inhibition of matrix metalloproteinase activity by TIMP-1 gene transfer effectively treats ischemic cardiomyopathy. Circulation, 2004, 110:SⅡ 180-186.
  • 5Hayashidani S, Tsutsui H, Ikeuchi M, et al. Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction.Am J Physiol Heart Circ Physiol, 2003 , 285:H1229-1235.
  • 6Bai P, Mabley J G, Liaudet L, et al. Matrix metalloproteinase activation is an early event in doxorubicin-induced cardiotoxicity. Oncol Rep, 2004 , 11:505-508.
  • 7Kim H E, Dalal S S, Young E, et al. Disruption of the myocardial extracellular matrix leads to cardiac dysfunction. J Clin Invest, 2000, 106: 857-866.
  • 8Siwik D A, Pagano P J, Colucci W S. Oxidative stress regulates collagen synthesis and matrix metalloproteinase activity in cardiac fibroblasts. Am J Physiol Cell Physiol , 2001,280 ; C53- C60.
  • 9Singal P K, Iliskovic N. Doxorubicin-induced cardiomyopathy. N EnglJ Med, 1998,339:900-905.
  • 10Siveski-Iliskovic N, Hill M, Chow D A, et al. Probucol protects against adriamycin cardiomyopathy without interfering with its antitumor effect. Circulation, 1995,91 : 10- 15.

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