辛伐他汀对心肌梗死大鼠心室重构与FoxO3a表达的影响

Effect of simvastatin on FoxO3a expression and ventricular remolding in rats with myocardial infarction

目的探讨辛伐他汀对大鼠心肌梗死后心室重构和FoxO3a表达的影响。方法建立大鼠MI模型,24 h后存活大鼠随机分成心肌梗死组(MI组,n=8)、辛伐他汀20 mg组[20 mg/(kg.d),Sim组,n=8],并同时建立假手术组(Sham组,n=10)。4周后观察心室质量指数(LVWI)、天狼猩红染色分析左室非梗死区胶原容积分数(CVF)、HE染色观察心肌组织病理改变,RT-PCR和Western blot检测FoxO3a在非梗死区mRNA和蛋白表达水平。结果 MI组较Sham组LVWI[(2.62±0.16)vs(1.80±0.13),P<0.05]、非梗死区Ⅰ型胶原容积分数[(18.81±2.65)vs(5.01±0.84),P<0.05]、Ⅲ型胶原容积分数[(3.83±0.38)vs(1.52±0.23),P<0.05]及Ⅰ/Ⅲ比值[(4.96±0.90)vs(3.31±0.40),P<0.05]显著增加;左室心肌非梗死区FoxO3a mRNA[(0.29±0.05)vs(0.57±0.06),P<0.05]与蛋白[(0.28±0.04)vs(0.62±0.07),P<0.05]表达均降低。与MI组相比,Sim组LVWI[(2.27±0.08)vs(2.62±0.16),P<0.05]、非梗死区I型胶原容积分数[(9.26±1.13)vs(18.81±2.65),P<0.05]、Ⅲ型胶原容积分数[(2.37±0.23)vs(3.83±0.38),P<0.05]及Ⅰ/Ⅲ比值[(3.98±0.79)vs(4.96±0.90),P<0.05]均显著下降;但高于Sham组(P<0.05);左室心肌非梗死区FoxO3a mRNA[(0.49±0.06)vs(0.29±0.05),P<0.05]与蛋白[(0.38±0.08)vs(0.28±0.04),P<0.05]表达均显著增高;但低于Sham组(P<0.05),心肌组织病理结构得到改善。结论辛伐他汀能有效改善MI后心肌损伤和心室重构,其机制可能与其在基因转录和蛋白质翻译水平促进FoxO3a表达综合作用有关。

Objective To study the effect of simvastatin on ventricular remodeling and FoxO3a expression in rats with myocardial infarction（MI）.Methods After a MI model of rats was established,24 survived rats were randomly divided into MI group（n=8）,simvastatin treatment group（n=8） and sham-operation group（n=10）.After 4 weeks,left ventricular weight index（LVWI） and collagen volume fraction（CVF） were detected in non-infarction zone（NIZ） with Picric-Sirius red staining.mRNA and protein expression of FoxO3a in NIZ was detected by reverse transcription polymerase chain reaction（RT-PCR） and Western blotting.Myocardial histopathology was examined with HE staining.Data were analyzed with the SAS 9.1 statistical software.Results The LVWI,types I and III CVF,and their ratio in NIZ were significantly higher in MI group than in sham operation（2.62±0.16 vs 1.80±0.13,18.81±2.65 vs 5.01±0.84,3.83±0.38 vs 1.52±0.23,and 4.96±0.90 vs 3.31±0.40,P0.05）.The mRNA and protein expression level of FoxO3a in NIZ was significantly lower in MI group than in sham operation（0.29±0.05 vs 0.57±0.06,0.28±0.04 vs 0.62±0.07,P0.05）.The LVWI,types Ⅰ and Ⅲ CVF,and their ratio in NIZ were significantly lower in simvastatin treatment group than in MI group（2.27±0.08 vs 2.62±0.16,9.26±1.13 vs 18.81±2.65,2.37±0.23 vs 3.83±0.38,and 3.98±0.79 vs 4.96±0.90,P0.05）,which were higher than those in sham operation group（P0.05）.The mRNA and protein expression level of FoxO3a in NIZ was significantly higher in simvastatin treatment group than in MI group（0.49±0.06 vs 0.29±0.05,0.38±0.08 vs 0.28±0.04,P0.05）,which was lower than that in sham operation（P0.05）.The improvement in lesions of myocardial tissue was better in simvastatin treatment group than in MI group（P0.05）.Conclusion Simvastatin can effectively improve the ventricular remodeling in rats with MI.The mechanism of simvastatin may be related with its role in up-regulation of FoxO3a expression at gene transcription and protein translation level.