瑞舒伐他汀联合厄贝沙坦对大鼠心肌肥厚性重构的影响

Effect of rosuvastatin combined with irbesartan on remodeling of myocardial hypertrophy in rats

目的:探讨瑞舒伐他汀联合厄贝沙坦对心肌肥厚大鼠心室重构的影响。方法:SPF级体重240~300 g雄性SD大鼠50只随机分为对照组、模型组、瑞舒伐他汀组、厄贝沙坦组和联合组。除对照组外,其余4组大鼠连续14 d给予皮下注射异丙肾上腺素(2.5 mg/kg)。自造模当天开始,对照组和模型组给予生理盐水灌胃,瑞舒伐他汀组、厄贝沙坦组和联合组分别给予瑞舒伐他汀(4 mg·kg^(-1)·d^(-1))、厄贝沙坦(15 mg·kg^(-1)·d^(-1))和瑞舒伐他汀(4 mg·kg^(-1)·d^(-1))+厄贝沙坦(15 mg·kg^(-1)·d^(-1))灌胃处理,连续干预4周。干预结束后,分别测定各组大鼠心脏质量指数、左室质量指数,HE染色观察心肌细胞肥大程度,RT-PCR测定肥大相关因子ANF、β-MHC和AT1受体(AT1R)的mRNA表达,Western blot法测定AT1R的蛋白表达。结果:与对照组相比,模型组的心脏质量指数、左室质量指数、ANF和β-MHC的mRNA表达均增加(P<0.05);与模型组相比,瑞舒伐他汀组和厄贝沙坦组的心脏质量指数、左室质量指数、ANF和β-MHC的mRNA表达均降低(P<0.05),联合组效果优于单药组(P<0.05)。瑞舒伐他汀组及厄贝沙坦组AT1R的mRNA及蛋白表达均低于模型组(P<0.05),而联合组AT1R的mRNA及蛋白表达水平低于各单独用药组(P<0.05)。结论:瑞舒伐他汀及厄贝沙坦均能不同程度地改善心肌肥厚。它们的抗心肌肥厚作用可通过下调AT1R的mRNA和蛋白表达实现。联合用药的效果优于单一药物。

AIM：To evaluate the effect of rosuvastatin combined with irbesartan on the remodeling of myocardial hypertrophy in the rats.METHODS：Male SD rats（ n = 50） were randomly divided into control group,model group,rosuvastatin group,irbesartan group and combination group.The model of myocardial hypertrophy was established by subcutaneous injection of isoproterenol at dose of 2.5 mg/kg for 14 d.From the first day of modeling,the rats in control group and model group received intragastrical saline,and the rats in rosuvastatin group,irbesartan group and combination group were treated with rosuvastatin（ 4 mg·kg^-1·d^-1）,irbesartan（ 15 mg·kg^-1·d^-1） and rosuvastatin（ 4 mg·kg^-1·d^-1） ＋ irbesartan（ 15 mg·kg^-1·d^-1）,respectively.The interventions continued for 4 weeks.After the interventions,the cardiac mass index and left ventricular mass index of the SD rats were measured.Besides,the degree of myocardial hypertrophy was observed with HE staining.The mRNA expression of hypertrophy-related factors,such as ANF,β-MHC and AT1 R was determined by RT-PCR,and the protein expression of AT1 R was determined by Western blot.RESULTS：Compared with control group,the cardiac mass index,left ventricular mass index,as well as the mRNA expression of ANF and β-MHC in model group were significantly increased（ P〈 0.05）.Compared with model group,the above factors in rosuvastatin group and irbesartan group were decreased（ P〈 0.05）,and the factors in combination group were lower than those in rosuvastatin group and irbesartan group（ P〈 0.05）.In addition,the expression of AT1 R at mRNA and protein levels in rosuvastatin group and irbesartan group was lower than that in model group（ P〈 0.05）,while the expression AT1 R at mRNA and protein levels in combination group was lower than that in rosuvastatin group and irbesartan group（ P〈 0.05）.CONCLUSION：Rosuvastatin and irbesartan are equally effective drugs to resist the formation of myocardial hypertrophy by decreasing the expression of AT 1R.Moreover,combination of the 2 drugs is more effective to improve the degree of myocardial hypertrophy than the 2 drugs alone.