心肌纤维化可导致心脏舒缩功能受损,是许多心脏疾病的终末阶段。他汀类药物可通过减少巨噬细胞浸润、降低炎症细胞因子表达发挥抗炎作用;抑制氧化应激、提高NO的生物利用度来改善内皮功能;抑制肾素-血管紧张素-醛固酮系统活性及相关神经内分泌激素激活;抑制AngⅡ、TGF-β1刺激的成纤维细胞增殖、心脏Ⅰ型和Ⅲ型胶原mRNA的表达;最终发挥抗心肌纤维化的作用。作者就他汀类药物在抗炎、改善内皮功能、抑制神经内分泌激素激活、抑制心肌成纤维细胞增殖及胶原蛋白过度沉积等方面的研究作一综述。

[1] 赵桂琴,吴国球,刘乃丰.心肌肌钙蛋白I异常病人血清结缔组织生长因子表达的研究[J].东南大学学报:医学版,2007,26(3):166-169.
[2] 何立峰,马礼坤.阿托伐他汀对实验性大鼠心肌纤维化的干预作用及可能机制[J].中国病理生理杂志,2010,26(2):227-232.
[3] NISHIOKA T,SUZUKI M,ONISHI K,et al.Eplerenone attenuatesm yocardial fibrosis in the angiotensin Ⅱ- induced hypertensive mouse:involvement of tenascin-C induced by aldosterone- mediated inflammation[J].J Cardiovasc Pharmacol,2007,49(5):261-268.
[4] ANDRAE J,GALLINI R,BETSHOLTZ C.Role of platelet-derived growth factors in physiology and medicine[J].Genes Dev,2008,22(10):1276-1312.
[5] TAKANO H,ZOU,Y,HASEGAWA H,et al.Oxidative stress-induced signal transduction pathways in cardiac myocytes:involvement of ROS in heart diseases[J].Antioxid Redox Signal,2003,5(6):789-794.
[6] YASUNARI K,MAEDA K,MINAMI M,et al.HMG-CoA reductase inhibitors pre-vent migration of human coronary smooth muscle cells through suppression of increase in oxidative stress[J].Arterioscler Thromb Vasc Biol,2001,21:937-942.
[7] CASTRO C,DIEZ-JUAN A,CORTES,M J,et al.Distinct regulation of mitogen-activated protein kinases and p27Kip1 in smooth muscle cells from different vascular beds.A potential role in establishing regional phenotypic variance[J].Biol Chem,2003,278:4482-4490.
[8] TEA B S,DAM T V,MOREAU P,et al.Apoptosis during regression of cardiac hypertrophy in spontaneously hypertensive rats.Temporal regulation and spatial heterogeneity[J].Hyper-tension,1999,34(2):229-235.
[9] BUEMI M,CORICA F,MARINO D,et al.Cardiovascular remodeling,apoptosis,and drugs[J].Am J Hypertens,2000,13:450-454.
[10] YAN C,KOJI O,MIZUKI M,et al.Differential impact of atorvastatin vs pravastatin on progressive insulin resistance and left ventricular diastolic dysfunction in a rat model of type Ⅱ diabetes[J].Circ J,2007,71:144-152.
[11] DAVIGNON J.Beneficial cardiovascular pleiotropic effects of statins[J].Circulation,2004,109:39-43.
[12] IWATA M,MATURANA A,HOSHIJIMA M,et al.PKCε–PKD1 signaling complex at Z-discs plays a pivotal role in the cardiac hypertrophy induced by G-protein coupling receptor agonists[J].Biochem Biophys Res Commun,2005,327:1105-1113.
[13] VEGA R B,HARRISON B C,MEADOWS E,et al.Protein kinases C and D mediate agonist-dependent cardiac hypertrophy through nuclear export of histone deacetylase 5[J].Mol Cell Biol,2004,24:8374-8385.
[14] HAWORTH R S,ROBERTS N A,CUELLO F,et al.Regulation of protein kinase D activity in adult myocardium:novel counter-regulatory roles for protein kinase c epsilon and protein kinase A[J].J Mol Cell Cardiol,2007,43:686-695.
[15] McENEANEY V,HARVEY B J,THOMAS W.Aldosterone rapidly activates protein kinase D via a mineralocorticoid receptor/EGFR trans-activation pathway in the M1 kidney CCD cell line[J].J Steroid Biochem Mol Biol,2007,107:180-190.
[16] ROMERO D G,WELSH B L,GOMEZ-SANCHEZ E P,et al.Angiotensin Ⅱ-mediated protein kinase d activation stimulates aldosterone and cortisol secretion in H295R human adrenocortical cells[J].Endocrinology,2006,147:6046-6055.
[17] KIM Y,PHAN D,van ROOIJ E,et al.The MEF2D transcription factor mediates stress-dependent cardiac remodeling in mice[J].J Clin Invest,2008,118:124-132.
[18] MARTIN J,DENVER R,BAILEY M,et al.In vitro inhibitory effects of atorvastatin on cardiac fibroblasts:implications for ventricular remodeling[J].Clin Exp Pharmacol Physiol,2005,32:697-701.
[19] SAITOH T,NAKAJIMA T,KAWAHARA K.Possible involvement of apoptotic death of myocytes in left ventricular remodeling after myocardial infarction[J].Jpn J Physiol,2003,53:247- 252.
[20] DECHEND R,FIEBELER A,PARK J K,et al.Amelioration of angiotensin Ⅱ-induced cardiac injury by a 3-hydroxy-3-methyl-glutaryl coenzyme a reductase inhibitor[J].Circulation,2001,104:576.
[21] PINTO Y M,PINTO-SIETSMA S J,PHILIPP T,et al.Reduction in left ventricular messenger RNA for transforming growth factor beta(1)at tenuates left ventricular fibrosis an d improves survival without lowering blood pressure in the hypertensive TGR(mRen2 )27 Rat[J].Hypertension,2000,36:747-754.
[22] BROOKS W W,CONRADC H.Myocardial fibros is intransforming growth factor beta(1)eterozygous mice[J].Mol Cell Cardiol,2000,32:187-195.
[23] 谭安雄,王玉银,李金成.阿托伐他汀对自发性高血压大鼠心室重构的影响[J].中国医院药学杂志,2008,28(4):274-276.
[24] 何文静,张英杰.他汀类药物对心肌梗死后心室重构的作用[J].中国心血管病研究,2007,5(10):791-793.
[25] LOPEZ B,QUEREJETA R,VARO N,et al.Usefulness of serum carboxyterminal propeptide of procollagen type I in assessment of the cardio reparative ability of antihypertensive treatment in hypertensive patients[J].Circulation,2001,104(3):286- 291.
[26] 王焕,蔡恒.阿托伐他汀对轻度胆固醇升高的高血压心肌纤维化的影响[J].药物与临床,2010,48(32):44-46.