瑞舒伐他汀对急性心肌梗死大鼠心肌重构的作用及其机制

Effect of rosuvastatin on myocardial remodeling and mechanism in rats with acute myocardial infarction

目的探讨瑞舒伐他汀对急性心肌梗死(AMI)大鼠心肌重构的作用及其机制。方法选择健康成年雄性SD大鼠60只,通过结扎冠状动脉左前降支建立AMI大鼠模型51只,按照随机数表法分成假手术组、模型组和他汀组,每组各17只。他汀组大鼠灌胃给药瑞舒伐他汀钙片10 mg/(kg·d),1/日,另外两组大鼠给予等量的蒸馏水,连续给药6周。采用彩色多普勒超声诊断仪检测左室射血分数(LVEF)、左室舒张末期内径(LVEDD)及左室收缩末期内径(LVESD)。应用RT-PCR技术检测心肌组织基质金属蛋白酶-2/9/10(MMP2/9/10)、Perionstin蛋白及转化生长因子-β1(TGF-β1)m RNA表达情况。结果模型组和他汀组大鼠的LVEDD及LVESD均明显高于假手术组,LVEF显著低于假手术组,差异均具有统计学意义(P均<0.05)。与模型组相比,他汀组大鼠的LVEDD及LVESD明显下降,LVEF显著升高,差异均具有统计学意义(P均<0.05)。与假手术组相比,其余两组大鼠心肌组织中MMP-2/9/10、Perionstin蛋白及TGF-β1的m RNA表达均明显升高;其中他汀组大鼠心脏中MMP2/9/10、Perionstin蛋白及TGF-β1的m RNA表达显著低于模型组,且差异均具有统计学意义(P均<0.05)。药物干预结束后,假手术组大鼠存活率为76.47%(13/17)明显高于模型组的41.18%(7/17)和他汀组的64.71%(11/17),同时他汀组的存活率显著高于模型组,且差异均具有统计学意义(P均<0.05)。结论瑞舒伐他汀可改善AMI大鼠心脏功能,可能通过调节MMP2/9/10、Perionstin蛋白及TGF-β1的m RNA表达来调控其心肌重构。

Objective To discuss the effect of rosuvastatin on myocardial remodeling and mechanism inrats with acute myocardial infarction （AMI）. Methods Male adult SD rats （n=60） were chosen and AMI modelwas established in 51 rats through ligating left coronary anterior descending branch, and then they were randomlydivided into sham-operation group, model group and rosuvastatin group （each n=17）. The rosuvastatin groupwas intragastrically given rosuvastatin calcium tablets [10 mg/（kg·d）] once a day, and other 2 groups weregiven distilled water in the same dose for 6 w. The left ventricular ejection fraction （LVEF）, left ventricular enddiastolicinner diameter （LVEDd） and left ventricular end-systolic diameter （LVESd） were detected by using colorDoppler ultrasonic diagnostic apparatus. The mRNA expressions of myocardial matrix metalloproteinase-2/9/10（MMP-2/9/10）, Perionstin protein and transforming growth factor β1 （TGF-β1） were detected by using reversetranscription polymerase chain reaction （RT-PCR）. Results LVEDd and LVESd were significantly higherand LVEF was significantly lower in model group and rosuvastatin group than those in sham-operation group（all P〈0.05）. Compared with model group, LVEDd and LVESd decreased significantly and LVEF increasedsignificantly in rosuvastatin group （all P〈0.05）. Compared with sham-operation group, the mRNA expressions ofMMP-2/9/10, Perionstin protein and TGF-β1 increased significantly in other 2 groups, and were significantlylower in rosuvastatin group than those in model group （all P〈0.05）. After drug intervention finished, the survivalrate of rat was 76.47% （13/17） in sham-operation group, which was significantly higher than that in model group[41.18% （7/17）] and rosuvastatin group [64.71% （11/17）], and meanwhile, the survival rate of rat was significantlyhigher in rosuvastatin group than that in model group （all P〈0.05）. Conclusion Rosuvastatin can improve heartfunction and control myocardial remodeling through regulating the mRNA expressions of MMP-2/9/10, Perionstinprotein and TGF-β1.