辛伐他汀对心肌梗死大鼠心肌中基质金属蛋白酶9表达影响.docVIP

辛伐他汀对心肌梗死大鼠心肌中基质金属蛋白酶9表达影响【摘要】目的 观察辛伐他汀对心肌梗死大鼠心肌中基质金属蛋白酶9表达的影响,探讨辛伐他汀降脂效应以外,对改善心肌梗死大鼠心功能与心室重构的作用机制。方法 34只大鼠分3组:(1)MI组:仅结扎左冠状动脉前降支(LAD);(2)治疗组(MI-S):结扎LAD,并用辛伐他汀40mgkg-1?d-1进行灌胃;(3)假手术组(SH):开胸,但不结扎LAD。4周后检测三组大鼠血流动力学指标及心肌中基质金属蛋白酶9(MMPs-9). 结果 MI组与SH组相比,血流动力学指标有明显差异(P 基质金属蛋白酶可能介入心肌梗死愈合过程的几个方面,包括早期细胞外基质的降解,炎细胞和纤维母细胞的迁移,血管生成,新合成的结缔组织的重塑和生长因子活性的调节。在本实验中,通过辛伐他汀干预后,心室肌细胞中MMP-9的表达降低了,说明辛伐他汀在心室重构的作用中,抑制MMP-9的表达是其机制之一,具体机理还有待进一步研究。 参考文献 [1]Indolfi C,Di Lorenzo E,Perrino C,et al.Hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin prevents cardiac hypertrophy induced by pressure overload and inhibits p21ras activation.Circulation.2002;106(16):2118-24. [2]Lee TM,Chou TF,Tsai CH.Effects of pravastatin on cardiomyocyte hypertrophy and ventricular vulnerability in normolipidemic rats after myocardial infarction.J Mol Cell Cardiol.2003;35(12):1449-59. [3]Oi S,Haneda T,Osaki J,et al.Lovastatin prevents angiotensin II-induced cardiac hypertrophy in cultured neonatal rat heart cells.Eur JPharmacol.1999;376(1-2):139-48. [4]Porter KE,Turner NA,O’Regan DJ,et al.Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA.Cardiovasc Res.2004;61(4):745-55. [5]Hayashidani S,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.Circulation.2002;105(7):868-73. [6]Patel R,Nagueh SF,Tsybouleva N,et al.Simvastatin induces regression of cardiac hypertrophy and fibrosis and improves cardiac function in a transgenic rabbit model of human hypertrophic cardiomyopathy.Circulation.2001;104(3):317-24. [7]Diwan A,Tran T,Misra A,Mann DL。Inflammatory mediators and the failing heart:a translational approach.Curr Mol Med.2003;3(2):161-82. [8]Ferro D,Parrotto S,Basili S,et al.Simvastatin inhibits the monocyte expression of proinflammatory cytokines in patients with hy