辛伐他汀对大鼠心肌梗死后心室重构的影响及其与TGF-β_1/TAK1信号转导的相关性  

Effects of simvastatin on ventricular remodeling after myocardial infarction induced by TGF-β_1/TAK1 pathway in rat

作　　者：肖祥彬[1] 覃数[1] 张冬颖[1] 马康华[1] 

机构地区：[1]重庆医科大学附属第一医院心血管内科,重庆400016

出　　处：《解放军医学杂志》2009年第9期1085-1088,共4页Medical Journal of Chinese People's Liberation Army

基　　金：重庆市自然科学基金资助项目[渝科发计字(2004)54号文]

摘　　要：目的探讨辛伐他汀对大鼠心肌梗死后心室重构的影响及其可能机制。方法建立大鼠心肌梗死模型,将24h后存活大鼠随机分成心肌梗死组(MI组,n=9)、辛伐他汀10mg组[10mg/(kg.d),Si m1组;n=8]、辛伐他汀20mg组[20mg/(kg.d),Si m2组;n=10]、辛伐他汀40mg组[40mg/(kg.d),Si m4组;n=9]。另设假手术组(Sham组,n=10)。4周后观察大鼠血脂水平,血流动力学指标,左室重量指数,HE染色观察心肌组织结构的变化,计算心肌细胞横切面面积。采用Western blotting和RT-PCR检测转化生长因子β1(TGF-β1)和TGF-β活化激酶1(TAK1)在非梗死区的表达。结果与MI组比较,各Si m组的血流动力学指标、左心室重量指数、心肌细胞横切面面积及病理学变化均有明显改善,TGF-β1和TAK1的mRNA和蛋白表达均明显下调。Si m2组和Si m4组的前述指标较Si m1组均有改善(P<0.05),但Si m2组与Si m4组间无统计学差异(P>0.05)。各组血脂水平均无统计学差异(P>0.05)。结论辛伐他汀可以抑制大鼠心肌梗死后心室重构,在20mg/(kg.d)以内增加辛伐他汀的剂量可以增强其疗效。辛伐他汀的这种作用与其调脂作用无关,可能与其抑制TGF-β1/TAK1信号转导有关。Objective To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and the possible mechanisms involved. Methods The myocardial infarction rat model was reproduced. Twenty-four hours after infarction, the survived rats were randomly divided into myocardial infarction group （MI group, n=9）, simvastatin 10mg group [10mg/（kg · d）, Siml group; n= 8], simvastatin 20mg group [20mg/（kg · d）, Sim2 group; n= 10] and simvastatin 40mg group [40mg/（kg · d）, Sire4 group; n=9]. A sharrroperated group （Sham group; n=10） served as control. Four weeks later, the serum lipid level, hemodynamic indexes and left ventricular weight index （LVWI） were measured. The changes in rats＇ myocardial tissue were observed with HE staining; the cros-sectional area of myocardial cells was calculated. The expressions of transforming growth factor β1 （TGF -β1） and TGF -β- activated kinase 1（TAK 1） in non-infarction area were determined by Western blotting and reverse transcription polymerase chain reaction （RT PCR）. Results The hemodynamic indexes, LVWI, cross-sectional area of myocardial cells and the pathological changes were improved, and mRNA and protein expressions of TGF β1 and TAK1 were down-regulated significantly in the 3 Sire-treated groups compared with that in MI group. The indices mentioned above were significantly different in Sire2 and Sim4 group compared with Sire4 group （P〈0. 05）, while no significant difference was found in serum lipid levels among all the groups （P〉0. 05）. Conclusion The inhibitory effect of simvastatin on ventricular remodeling after acute myocardial infarction is independent of its lipid-regulating effect, but possibly attributed to its action in inhibiting the TGF- β1/AK1 signal transduction. Within the concentration of 20mg/（kg · d）, the therapeutic efficacy of simvastatin may be more obvious with an increase in its dosage.

关 键 词：辛伐他汀 心肌梗死 心室重构 转化生长因子Β1 TGF-β活化激酶1 

分 类 号：R542.22[医药卫生—心血管疾病]