沙库巴曲缬沙坦对心肌梗死大鼠模型心肌重构和心功能的影响  

Effects of Sacubitril/Valsartan on myocardial remodeling and cardiac function in rats with myocardial infarction

作　　者：卢辉耀[1] 徐训发[1] 郭佳音 赵文安[1] 林志民[1] 赖文文 Lu Huiyao;Xu Xunfa;Guo Jiayin;Zhao Wenan;Lin Zhimin;Lai Wenwen(Department of Cardiovascular,the Second Affiliated Hospital of Fujian Medical University,Fuzhou 362000,China)

机构地区：[1]福建医科大学附属第二医院心血管内科,福州362000

出　　处：《中华老年医学杂志》2019年第9期1048-1052,共5页Chinese Journal of Geriatrics

摘　　要：目的探讨沙库巴曲缬沙坦对心肌梗死模型大鼠心肌重构和心功能的影响及其机制。方法本研究分为体内急性心肌梗死(AMI)大鼠模型和体外细胞实验。大鼠模型部分:将60只SPF级雄性大鼠,结扎冠状动脉前降支建立心肌梗死模型,1周后用随机数表法分为沙库巴曲缬沙坦组(30只)和模型组(30只),分别灌胃给予沙库巴曲缬沙坦68 mg/kg和溶媒(生理盐水),每日1次,共4周。最后1次给药后24 h,超声心动图检查大鼠左心室心功能、光镜下观察左心室病理变化,苦味酸-天狼猩红染色法定量分析心肌纤维化程度。体外细胞实验部分:制备同样品种幼鼠心脏的心肌细胞及成纤维细胞,分为模型组、AngⅡ组、LBQ657(脑啡肽酶抑制剂)组和valsartan组、LCZ696组,用3H-亮氨酸掺入法和3H-脯氨酸掺入法检测心肌细胞肥大及纤维化程度。结果用药前两组大鼠左心室功能各指标的差异无统计学意义(P>0.05),用药4周后,沙库巴曲缬沙坦组大鼠的左心室舒张期末直径及左心室收缩期末容积显著小于模型组[(9.73±0.26)mm比(10.52±0.21)mm,P<0.05,(0.19±0.03)ml比(0.31±0.02)ml,P<0.01];左心室射血分数大于模型组[(60.17±2.18)%比(47.16±5.14)%,P<0.01]。沙库巴曲缬沙坦组大鼠梗死区心肌细胞损伤程度低于模型组,沙库巴曲缬沙坦组大鼠非梗死区及梗死区周边的心肌纤维化面积小于模型组[非梗死区:(4.0±0.1)%比(6.1±0.8)%,P<0.001;梗死区周边:(15.7±0.8)%比(23.8±1.2)%,P<0.001]。体外培养心肌细胞实验见:valsartan组心肌成纤维细胞3H-脯氨酸渗入量低于AngⅡ组[(152.77±8.46)CPM比(221.87±13.41)CPM,P<0.01],心肌细胞3H-亮氨酸渗入量低于AngⅡ组[(113.47±2.33)CPM比(127.65±2.38)CPM,P<0.01],LBQ657组心肌细胞3H-亮氨酸渗入量低于AngⅡ组[(119.78±2.98)CPM比(127.65±2.38)CPM,P<0.05],联合应用能进一步减轻心肌肥大与纤维化(P<0.05)。结论沙库巴曲缬沙坦可有效缓解心梗后心肌重塑及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,AngⅡgroup,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 Va

关 键 词：心肌梗死 大鼠 沙库巴曲缬沙坦 心室重构 心脏功能试验 

分 类 号：R542.22[医药卫生—心血管疾病]