阿托伐他汀对心肌肥厚大鼠细胞外基质重塑的抑制作用(英文)  

Inhibitory Effect of Atorvastatin on Cardiac Hypertrophy and Extracellu lar Matrix Remodeling in Rats

作　　者：白江涛[1] 陆凤翔[1] 许迪[1] 陈莉[1] 周蕾[1] 雍永宏[1] 

机构地区：[1]南京医科大学第一附属医院心脏科,江苏南京210029

出　　处：《高血压杂志》2004年第5期447-451,共5页Chinese Journal of Hypertension

摘　　要：目的　探讨阿托伐他汀对去甲肾上腺素诱导的心肌肥厚大鼠细胞外基质重塑的影响及其可能的机制。方法　雄性SD大鼠随机分为三组 :(1)对照组 ,(2 )去甲肾上腺素组 [1 0 6mg/ (kg·d)× 15d],(3)去甲肾上腺素 +阿托伐他汀组 [5 0mg/ (kg·d)× 15d]。去甲肾上腺素ip ,2次 /d ,15d ,建立心肌肥厚模型。应用超声心动图及病理学方法评价整体心肌肥厚及组织胶原表达。用逆转录-聚合酶链反应法 (RT PCR)及免疫组化检测细胞外基质调节因子 -基质金属蛋白酶 (MMP - 9)及其生理性抑制剂 (TIMP 1)和转化生长因子 β1(TGF - β1)mRNA和蛋白表达。结果　去甲肾上腺素组大鼠发生左心室肥厚及纤维化 ,胶原含量及MMP 9、TIMP 1和TGF - β1蛋白、mRNA表达显著高于健康对照组 (P <0 0 1)。阿托伐他汀能减少心肌中总体胶原及Ⅰ、Ⅲ型胶原的合成及MMP 9、TGF - β1表达 (P <0 0 1)。结论　MMP 9、TIMP 1和TGF - β1与心肌肥厚大鼠的细胞外基质重塑有关。阿托伐他汀能有效防治心肌纤维化及细胞外基质重塑 ,这一效应与其降低心肌中高表达的MMP 9和TGF - β1有关。Objective To investigate the effect and mechanisms of atorvastatin on norepinephrine-induced cardiac hypertrophy and extrac ellular matrix remodeling in rats. Methods Male SD rats were randomLy allocated into three groups:(1)control(\%n\%=8), (2)norepinephrine[106 mg/(kg·d)×15 d](\%n\%=8), (3)norepinephrine+atorvastatin[50 mg/(kg·d)×15 d] (\%n\%=8). The hypertension model was established by norepinephrine injected intraperi toneally Bid for 15 days. Cardiac hypertrophy and extracellular matrix remodeli ng were evaluated by echocardiography and morphological examination. The mRNA and protein expres sion of matrix metalloproteinase(MMP 9), tissue inhibitor of metalloproteinase(TIMP 1) and transforming growth factor β 1(TGF β 1)were examined by reverse transcription polymerase chain reaction(RT PCR) and immunohistochemical analysis. Results NE-induced hypertrophy and extracellule matrix remodeling was shown predominantly in left ventricle. mRNA and protein expression of MMP-9, TIMP-1 and TGF-β\-1 were increased (\%P\%< 001). After atorvastatin treatment, the total collagen and type Ⅰ, type Ⅲ collagen and the expression of MMP-9 and TGF-β\-1 were decreasd(\%P\%<001). Conclusion MMP-9, TIMP-1 and TGF-β\-1 are involved in cardiac extracellular matrix remodeling induced by NE. Atorvastatin prevented the cardiac fibrosis and extracellular matrix remodeling, and b lunted the increase of myocardial MMP-9 and TGF-β\-1.

关 键 词：阿托伐他汀 心肌肥厚 大鼠 细胞外基质 抑制作用 

分 类 号：R965[医药卫生—药理学]