Effects of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction / 中华老年医学杂志

ABSTRACT

Objective@#To explore the effect and mechanism of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction.@*Methods@#The acute myocardial infarction (AMI) rat model was established by ligating anterior descending branch of coronary artery for one week.A total of 60 adult male rats in SPF grade with AMI were randomized into the Sacubitril/Valsartan group and the model group, who were gavaged with Sacubitril/Valsartan (68 mg/kg, once daily, n=30) versus with normal saline once daily(n=30) for 4 weeks.Twenty-four hours after the last treatment, the left ventricular cardiac function was examined by echocardiography, and pathological changes of the left ventricle were observed under light microscope.The degree of myocardial fibrosis was quantitatively analyzed by picric acid-sirius scarlet staining.Myocardial cells and fibroblasts from rat pups of the same species were prepared in vitro and were divided into the control group, AngⅡ group, LBQ657 group, valsartan group and LCZ696 group.3[H]-leucine incorporation and 3[H]-proline incorporation were used to detect the myocardial hypertrophy and fibrosis.@*Results@#There was no significant difference in left ventricular function between the the model group and the Sacubitril/Valsartan group before medication (P>0.05). Four weeks after administration of the medications, end-diastolic diameter of left ventricle and end-systolic volume of left ventricle were lower [(9.73±0.26) mm vs.(10.52±0.21) mm, P<0.05; (0.19±0.03) ml vs.( 0.31±0.02) ml, P<0.01], and the left ventricular ejection fraction was higher [(60.17±2.18)% vs.(47.16±5.14)%, P<0.01] in the Sacubitril/Valsartan group than in the model group.The degree of myocardial cell injury in the infarct area was lower, and the area of myocardial fibrosis in the non-infarct zone and peripheral infarcted zone were less in the Sacubitril/Valsartan group than in the model group [(4.0±0.1)% vs. (6.1±0.8)%, P<0.001; (15.7±0.8)% vs. (23.8±1.2)%, P<0.001].3[H]-proline incorporation in cardiac fibroblasts was lower in the Valsartan group than in the Ang Ⅱ group [(152.77±8.46) CPM vs.(221.87±13.41) CPM, P<0.01].3[H]-leucine incorporation in myocardial cells was lower in the Valsartan group than in the Ang Ⅱ group [(113.47±2.33) CPM vs.(127.65±2.38) CPM, P<0.01].3[H]-leucine incorporation in myocardial cells was lower in LBQ657 group than in the Ang Ⅱ group [(119.78±2.98) CPM vs.(127.65±2.38) CPM, P<0.05], and the combined application of valsartan and LBQ657 can further reduce myocardial hypertrophy and fibrosis (P<0.05).@*Conclusions@#Sacubitril/Valsartan can effectively alleviate myocardial remodeling and cardiac dysfunction after myocardial infarction, and the mechanism may be related to reducing AngⅡ-induced myocardial hypertrophy and myocardial fibrosis.