期刊文献+

心肌梗死大鼠非梗死区间质纤维化及机制探讨 被引量:1

Study of Interstitial Fibrosis and Its Mechanism in Rats With Myocardial Infarction in Non-Infarct Zone
在线阅读 下载PDF
导出
摘要 目的:探讨心肌梗死后不同阶段非梗死区心肌胶原的变化及其发生机制。方法:雌性Wistar大鼠,通过结扎左冠状动脉前降支制备心肌梗死模型。分为心肌梗死组(最终存活32只)和假手术组(最终存活47只),于术后24h、1周、2周及4周随机从两组中各取10~12只大鼠,分别行病理组织学、心肌胶原容积密度分数(CVF)、肿瘤坏死因子-α(TNF-α)、基质金属蛋白酶-9(MMP-9)、血管紧张素Ⅱ(AngⅡ)和醛固酮(ALd)水平的分析,以及Ⅰ型胶原(col-1)及Ⅲ型胶原(col-3)的信使核糖核酸(mRNA)检测。结果:大鼠梗死范围为24%~33%。心肌组织Messon染色显示,假手术组间质只可见散在亮绿色胶原;术后24h^1周,心肌梗死组间质亮绿色胶原与假手术组基本相似;术后2~4周最明显。肿瘤坏死因子-α的表达在梗死后1~4周显著增强。心肌血管紧张素Ⅱ水平术后1~4周,心肌梗死组均高于假手术组,有显著性差异(P<0.05~0.001)。心肌醛固酮含量术后2~4周,心肌梗死组也明显于高假手术组,有显著性差异(P<0.05~0.001)。Ⅰ型胶原mRNA水平术后2~4周心肌梗死组明显高于假手术组;Ⅲ型胶原mRNA水平术后1~4周心肌梗死组明显高于假手术组(P均<0.05)。基质金属蛋白酶-9表达无变化。结论:①大鼠心肌梗死2周后非梗死区出现明显间质纤维化。②非梗死区间质纤维化可能与局部肾素血管紧张素醛固酮系统激活后增加血管紧张素Ⅱ水平及肿瘤坏死因子-α上调有关。③大鼠心肌梗死后4周内非梗死区基质金属蛋白酶-9表达无明显变化。 Objective:To investigate the changes of interstitial collagen in non-infarct zone(NIZ) and elucidate the mechanisms of the changes in an infarcted rat model. Methods:The rats undergoing sham operation or left coronary artery ligation were killed 24 hours, 1,2 and 4 weeks after operation. Infarct size, interstitial collagen volume fraction ( CVF ), Tumor necrosis factor α ( TNF-α), Matrix metalloproteinase (MMP)-9,Ang Ⅱ and Aldosterone(ALD) were measured . Expression of genes encoding collagen type 1 and collagen type 3 were measured by reverse transeriptase-polymerase chain reaction(RT-PCR) methods. Results:The myocardial infarction(MI) group exhibited increased non-infarct zone in CVF from 2 to 4 weeks ( P 〈 0. 05 - 0. 01) . The levels of TNF-α and Ang Ⅱ were increased from 1 to 4 weeks(P〈0.05 -0.001).The level of ALD were increaed from 2 to 4 weeks( P 〈 0.05 - 0. 001 ). The gene expression of collagen type 1 was more obvious from 2 to 4 weeks(P〈0.05). The gene expression of collagen type3 was more obvious from 1 to 4 weeks (P〈0.05 -0.01).The change of MMP-9 was not obvious( P 〉0.05 ). Conclusion: There was interstitial fibrosis in non-iniarct zone at 14 days after MI in rats,which might be associated with augmentation of Ang Ⅱ due to the activation of RAAS and the upregulation of TNF-α. The MMP-9 in non-infarct zone had no changes within the 4 weeks.
出处 《中国循环杂志》 CSCD 北大核心 2007年第5期380-384,共5页 Chinese Circulation Journal
基金 辽宁省教育基金项目(2004D177)
关键词 心肌梗塞 胶原 肿瘤坏死因子 基质金属蛋白酶 大鼠 Myocardial infarction Collagen Tumor necrosis factor Matrix metalloproteinase Rats
  • 相关文献

参考文献10

  • 1See F,Kompa A,Martin J,et al.Fibrosis as a therapeutic target post-myocardial infarction.Curr Pharm Des,2005,11 (4):477-487.
  • 2Loftis MJ,Sexton D,Carver W,et al.Effects of collagen density on cardiac fibroblast behavior and gene expression.J Cell Physiol,2003,196(3):504-511.
  • 3李兴武.心肌梗死后的心室重构[J].国外医学(老年医学分册),2001,22(4):161-163. 被引量:3
  • 4Zannad F,Radauceanu A.Effect of MR blockade on collagen formation and cardiovascular disease with a specific emphasis on heart failure.Heart Fail Rev,2005,10(1):71-78.
  • 5Touyz RM.The role of angiotensin Ⅱ in regulating vascular structuraland functional changes in hypertension.Curr Hypertens Rep,2003,5 (2):155-164.
  • 6Gonzalez A,Lopez B,Diez J.Fibrosis in hypertensive heart disease:role of the renin-angiotensin-aldosterone system.Med Clin North Am,2004,88(1):83-97.
  • 7Flesch M,Hoper A,Dell'Italia L,et al.Activation and functional significance of the renin-angiotensin system in mice with cardiac restricted overexpression of tumor necrosis factor.Circulation,2003,108(5):598-604.
  • 8Gurantz D,Yndestad A,Halvorsen B,et al.Etanercept or intravenous immunoglobulin attenuates expression of genes involved in post-myocardial infarction remodeling.Cardiovasc-Res,2005,67(1):106-115.
  • 9Heeneman S,Cleutjens JP,Faber BC,et al.The dynamic extracellular matrix:intervention strategies during heart failure and atherosclerosis.J Pathol,2003,200(4):516-525.
  • 10Bosman FT,Stamenkovic I.Functional structure and composition of the extracellular matrix.J Pathol,2003,200(4):423-428.

二级参考文献4

  • 1[1]Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling-consensus paper from an international forum on cardiac remodeling. J Am Coll Cardiol, 2000;35:569~582
  • 2[2]Yousef ZR, Redwood SR, Marber MS. Postinfarction left ventricular remodelling:Where are the theories and trials leading us? Heart, 2000;83:76~80
  • 3[3]Marroquin OC, Lamas GA. Beneficial effects of an open artery on left ventricular remodeling after myocardial infarction. Prog Cardiovas Dis, 2000;42:471~483
  • 4[4]Mann DL. Mechanisms and models in heart failure; a combinatorial approach. Circulation, 1999;100:999~1008

共引文献2

同被引文献13

  • 1Zimmermann WH, Cesnjevar R. Cardiac tissue engineering: implications for pediatric heart surgery. Pediatr Cardiol, 2009, 30: 716-723.
  • 2Zhang H, Hou JF, Shen Y, et al. Low level laser irradiation precondition to create friendly milieu of infarcted myocardium and enhance early survival of transplanted bone marrow cells. J Cell Mol Med, 2010, 14: 1975-1987.
  • 3Zhou Q, Zhou JY, Zheng Z, et al. A novel vascularized patch enhances cell survival and modifies ventricular remodeling in a rat myocardial infarction model. J Thorac Cardiovasc Surg, 2010, 140: 1388-1396. el-3.
  • 4Zakharova L, Nural-Guvener H, Nimlos J, et al. Chronic heart failure is associated with transforming growth factor beta-dependent yield and functional decline in atrial explant-derived c-Kit+ cells. J Am Heart Assoc, 2013, 2: e000317.
  • 5Villa MT, Chang DW. Muscle and omental flaps for chest wall reconstruction. Thorac Surg Clin, 2010, 20: 543-550.
  • 6Saifzadeh S, Pourreza B, Hohbenaghi R, et aI. Autogenous greater omentum, as a free nonvascularized graft, enhances bone healing: an experimental nonunion model. J Invest Surg, 2009, 22: 129-137.
  • 7Hughes BG, Schulz R. Targeting MMP-2 to treat ischemic heart injury. Basic Res Cardiol, 2014, 109: 424.
  • 8Spinale FG, Coker ML, Heung LJ, et al. A matrix metalloproteinase induction/activation system exists in the human left ventricular myocardium and is upregulated in heart failure. Circulation, 2000, 102: 1944-1949.
  • 9Li YY, MeTiernan CF, Feldman AM. Interplay of matrix metaHoproteinases, tissue inhihitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovase Res, 2000, 46: 214-224.
  • 10Spina].e FG, Villarveal F. Targeting malrix metalloproteinases in heart disease: lessons from endogenous inhibitors. Bioehem Pharmaeol, 2014, 90: 7-15.

引证文献1

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部