辛伐他汀改善心室重构与转化生长因子β1/Smad3信号途径的实验研究

目的探讨辛伐他汀(simvastatin,Sim)对大鼠心肌梗死后心室重构的作用及其机制。方法建立大鼠心肌梗死模型,24 h后存活大鼠随机分成心肌梗死组(MI,n=9)、辛伐他汀10 mg组(10 mg.kg-1.d-1,Sim1,n=8)、20 mg组(20 mg.kg-1.d-1,Sim2,n=10)和40 mg组(40 mg.kg-1.d-1,Sim4,n=9),设假手术组(Sham,n=10)。4 wk后观察血脂水平、血流动力学指标、心室重量指数和左室非梗死区胶原容积分数,Western blot和RT-PCR检测转化生长因子β1和Smad3在非梗死区的表达。结果①各组血脂水平差异无统计学意义,MI组左室重量指数增加、非梗死区Ⅰ、Ⅲ型胶原容积分数及Ⅰ/Ⅲ比值均增加,左心室功能受损;Sim各组LVWI、非梗死区Ⅰ、Ⅲ型胶原容积分数及Ⅰ/Ⅲ比值下降(但仍高于Sham组),左心室功能明显改善。②MI组转化生长因子β1和Smad3表达明显增加,Sim各组表达则明显降低(但仍高于Sham组)。结论辛伐他汀能有效改善大鼠心肌梗死后心室重构和心功能,机制与其调脂作用无关,可能与其抑制TGF-β1/Smad3信号转导有关。

The experimental study of the benificial effects of simvastatin on ventriculaRremodeling induced by TGFβ1 via Smad3 signal pathway

Aim To investigate the beneficial effects of simvastatin on ventricular remodeling in rats after myocardial infarction and its possible mechanisms.Method Twenty-four hours after myocardial infarction by left anterior descending coronary artery ligation,the survival rats were randomly divided into myocardial infarction group(MI,n=9),simvastatin 10 mg·kg-1·d-1 treatment group(Sim1,n=8),simvastatin 20 mg·kg-1·d-1 treatment group(Sim2,n=10) and simvastatin 40 mg·kg-1·d-1 treatment group(Sim4,n=9).Sham-operated animals underwent identical surgery except for the coronary artery ligation(Sham,n=10).After 4 weeks,levels of serum lipids were measured.Effects of sinvastatin on ventricular remodeling were evaluated by detecting changes of left ventricular weight index(LVWI),the collagen volume fraction(CVF) in non-infarction zone(NIZ) with Picric-Sirius Red Polarimetry,and the expressions of transforming growth factor β1(TGF-β1) and Smad3 in NIZ by Western blot and RT-PCR.Results(1) There were no significant differences betweem groups in levels of serum lipids(P>0.05).Compared with those in Sham group,LVWI,the typeⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were increased significantly in MI group.Compared with those in MI group,the LVWI,the type ⅠCVF,type Ⅲ CVF andⅠ/Ⅲ ratio in NIZ were decreased significantly in Sim groups(but higher than those in Sham group).Compared with MI groups,left ventricular function in rats treated with simvastatin was also obviously improved.(2) Contrasted to those in MI group,the expressions of TGF-β1 and Smad3 were down-regulated in simvastatin treatment groups(but higher than those in Sham group).Conclusions Sim can ameliorate ventricular remodeling and ventricular function in rats induced by MI,and the mechanisms can be independent of its lipid-lowering and associated with inhibition of TGF-β1/Smad3 signal transduction.