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辛伐他汀减轻舒张功能不全心力衰竭大鼠心肌纤维化 被引量:2

The Protective Effect of Simvastatin on Myocardial Fibrosis of Rats with Diastolic Heart Failure
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摘要 目的探讨辛伐他汀对舒张功能不全心力衰竭(diastolic heart failure,DHF)大鼠心脏功能保护和心肌纤维化的影响。方法雄性SD大鼠30只,随机分为阴性对照组、DHF组、辛伐他汀组。采用腹主动脉缩窄建立DHF模型,阴性对照组只开腹和分离腹主动脉。辛伐他汀组大鼠术后经灌胃给予辛伐他汀2 mg/(kg.d),阴性对照组和DHF组大鼠给予同等量的生理盐水。4周末心脏超声检测心功能,颈动脉插管记录血流动力学,HE染色和Masson染色观察心肌组织病理结构的变化。结果心脏超声显示DHF组大鼠室间隔和左心室后壁厚度、E/A比值明显增高,血流动力学检测显示收缩压、舒张压、左心室收缩压、左心室舒张末压升高,左心室松弛时间常数延长,左心室内压最大下降速率下降,心脏指数和左心室质量指数增加。辛伐他汀使增加的室间隔和左心室后壁厚度、E/A、收缩压、舒张压、左心室收缩压、左心室舒张末压、心脏指数和左心室质量指数降低,左心室松弛时间常数缩短,左心室内压最大下降速率升高。HE染色和Masson染色显示,DHF组大鼠心肌组织间纤维组织和炎性细胞增多,心肌胶原面积与总面积的比值和壁内小动脉管腔周围胶原面积与管腔面积的比值在心肌组织中显著增加;辛伐他汀减轻DHF大鼠心肌组织间纤维化和炎性细胞浸润,降低心肌胶原面积与总面积的比值以及壁内小动脉管腔周围胶原面积与管腔面积的比值。结论辛伐他汀改善DHF大鼠心脏功能,此作用可能与减轻心室纤维化有关。 Aim To study the effect of simvastatin on cardiac fibrosis of rats with diastolic heart failure (DHF). Methods 30 SD rats were randomly divided into three groups: control group, DHF group and simvastatin group. DHF model was produced by abdominal aortic coarctation in the rats. The rats in simvastatin group were given simvastatin 2 mg/(kg d) by intragastric administration for 4 weeks, the others were treated with equal isotonic Na chloride. After 4 weeks, cardiac function and hemorheology were assessed by echocardiography and catheterization. HE and Masson stain- ings were applied to observe altered myocardial histopathology and myocardial fibrosis, respectively. Results In DHF group, IVS, LVPWT, LVMI, E/A ratio, SBP, DBP, LVSP, LVEDP, fiber tissue, ventricular perivascular collagen area (CA), inflammatory cell invasion and collagen volume fraction (CVF) were increased. Tau was prolonged and LV -dp/dtmax was decreased. While in simvastatin group E/A ratio, IVS, LVPWT, LVMI, SBP, DBP, LVSP, LVEDP, inflammatory cell invasion, fiber tissue, CA and CVF were significantly decreased, prolonged Tau was shortened, and LV - dp/dtmax was increased compared with DHF group. Conclusion Simvastatin improves cardiac diastolic function in rats with DHF by ameliorating myocardial fibrosis.
出处 《中国动脉硬化杂志》 CAS CSCD 北大核心 2012年第11期976-980,共5页 Chinese Journal of Arteriosclerosis
基金 国家自然科学基金资助(30900625)
关键词 辛伐他汀 舒张功能不全 心肌细胞 心肌纤维化 Simvastatin Diastolic Heart Failure Myocardial Cell Myocardial Fibrosis
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参考文献16

  • 1Owan TE, Hodge DO, Herges RM, et al. Trends in prevalence and outcome of heart failure with preserved ejection fraction[J]. N EnglJ Med, 2006, 355 (3):251-259.
  • 2Tehrani F, Morrissey R, Phan A, et al. Stalin therapy in patients with diastolic heart failure [J ]. Clin Cardiol, 2010, 33 (4) : E1-E5.
  • 3Fukuta H, Sane DC, Brucks S, et al. Statin therapy may be associated with lower mortality in patients with diastolic' heart failure: a preliminary report[ J ]. Circulation, 2005, 112 (3): 357-363.
  • 4Roik M, Scisto P, Kochanowski J, et al. Tako-tsubo-like transient left ventricular dysfunction-a new cause of dias- tolic heart failure [ J]. Int J Cardiol, 2008, 127 (2): e102-e104.
  • 5Kuwahara F, Kai H, Tokuda K, et al. Transforming growth factor-beta function blocking prevents myocardial fibrosis and diastolic dysfunction in pressure-overloaded rats [ J]. Circulation, 2002, 106 (1) : 130-135.
  • 6Bayorh MA, Ganafa AA, Eatman D, et al. Simvastatin and losartan enhance nitric oxide and reduce oxidative stress in salt-induced hypertension[J]. Am J Hypertens, 2005, 18 ( 11 ) : 1 496-502.
  • 7Reed AL, Tanaka A, Sorescu D, et al. Diastolic dysfunction is associated with cardiac fibrosis in the senescence-accelerated mouse [J]. Am J Physiol Heart Circ Physiol, 2011, 301 (3) : H 824-831.
  • 8Karaahmet T, Tigen K, Dundar C, et al. The effect of cardiac fibrosis on left ventricular remodeling, diastolic function, and N-terminal pro-B-type natriuretic peptide levels in patients with nonischemic dilated cardiomyopathy [ J ]. Echocardiography, 2010, 27 (8): 954-960.
  • 9Berk BC, Fujiwara K, Lehoux S. ECM remodeling in hypertensive heart disease [J]. J Clin Invest, 2007, 117 (3) : 568-575.
  • 10Sung-A Chang, Yong-Jin Kim, Hye-Won Lee, et al. Effect of rosuvastatin on cardiac remodeling, function,and progression to heart failure in hypertensive heart with established left ventricular hypertrophy [ J ]. Hyperten- sion, 2009, 54 (3) : 591-597.

二级参考文献37

  • 1王安才,成蓓,谢晓竟,徐浩.阿托伐他汀对自发性高血压大鼠心室重构的影响[J].中国临床药理学与治疗学,2004,9(8):880-884. 被引量:32
  • 2Kostenis E, Milligan G, Christopoulos A, el al. G-pzotein-coup1ed receptor mas is a physiological antagonist of the angiotensin Ⅱ type Ⅰ receptor [J]. Circulation, 2005, 111 (14): 1 806-813.
  • 3Rapacciuolo A, Esposito G, Caron K, et al. Important role of endogenous norepinephrine and epinephrine in the development of in vivo pressure-overload cardiac hypertrophy[J]. J Am Coll Cardiol, 2001,38: 876-882.
  • 4Yulin LIAO, Hui ZHAO, Akiko OGAI, et al. Atorvastatin slows the progtession of cardiac remodeling in mice with pressure overload and inhibits epidermal growth factor receptor activation [ J ]. Hypertens Res 2008, 31 : 335 -344.
  • 5Tallant EA, Ferrario CM, Gallagher PE. Angiotensin ( 1-7 ) inhibits growth of cardiac myocytes through activation of the MAS receptor[J]. AM J Physiol Heart Circ Physiol, 2005, 289 (4) : H1 560-566.
  • 6Rikitake Y, Kawashima S, Takeshita S, et al. Antioxidative properties of fluvastatio. An HMG-CoA recluctase inhibitor, contribute to prevention of atherosclerosis in cholesterol-fed rabbits [ J ]. Atherosclerosis, 2001, 154 (1) : 87-96.
  • 7Libby P. Moleclar bases of the acute coronary syndromes[J].Circulation,1995,91:2844-2850.
  • 8Lefer AM, Campbell B, Shin YK. Simvastatin preserves the ischemic-reperfused myocardium in normocholesterolemic rat hearts[J].Circulation,1999,100:178-184.
  • 9Endres M, Laufs U, Huang Z. Stroke protection by 3-hydroxy-3-methylglutaryl(HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase[J].Proc Natl Acad Sci USA,1998,95:8880-8885.
  • 10Hayashidani SJ, Tsutsui H, Shiomi T, et al. Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction[J].Circulation,2002,105:868-873.

共引文献13

同被引文献24

  • 1Kong P, Christia P, Frangogiannis NG. The pathogenesis of cardiac fibrosis[J]. Cell Mol Life Sei, 2014, 71 (4) : 549-574.
  • 2Sasaki H, Asanuma H, Fujita M, et al. Mefformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase [J]. Circulation, 2009, 119 (19) : 2 568-577.
  • 3Xiao H, Ma X, Feng W, et al. Mefformin attenuates cardiac fibrosis by inhibiting the TGF betal-Smad3 signalling pathway [J]. Cardio- vasc Res, 2010, 87 (3) : 504-513.
  • 4Teunissen BE, Smeets PJ, Willemsen PH, et al. Activation of PP-ARdelta inhibits cardiac fibroblast proliferation and the transdifferen- tiation into myofibroblasts [J].Cardiovasc Res, 2007, 75 ( 3 ) : 519-529.
  • 5UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)[J]. Lancet, 1998, 352 (9131) : 854-865.
  • 6Eurich DT, McAlister FA, Blackburn DF, et al. Benefits and harms of antidiabetic agents in patients with diabetes and heart failure : sys- tematic review[J]. BMJ, 2007, 335 (7618) : 497.
  • 7Yin M, van der Horst IC, van Melle JP, et al. Mefformin improves cardiac function in a nondiabetie rat model of post-MI heart failure [J]. Am J Physiol Heart Cire Physiol, 2011, 301 (2): H 459-468.
  • 8Leask A. Potential therapeutic targets for cardiac fibrosis : TGFbeta, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast aetivation[J]. Cire Res, 2010, 106 (11) : 1 675-680.
  • 9Musi N, Hirshman MF, Nygren J, et al. Metformin increases AMP-activated protein kinase activity in skeletal muscle of subjects with type 2 diabetes[J]. Diabetes, 2002, 51 (7) : 2 074-081.
  • 10Kristensen JM, Treebak JT, Schjerling P, et al. Two week of met- formin treatment induces AMPK-dependent enhancement of insu- lin-stimulated glucose uptake in mouse soleus muscle [J]. Am J Physiol Endocrinol Metab, 2014, 306 (10) : E1 099-109.

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