替格瑞洛对AMI后小鼠左心室重构及心功能的影响

Effects of Ticagrelor on Left Ventricular Remodeling and Cardiac Function After AMI in Mice

目的探究替格瑞洛对急性心肌梗死(acute myocardial infarction,AMI)后小鼠左心室重构及心功能的影响。方法8周龄雄性C57BL/6小鼠随机分为5组:假手术组(Sham组)、AMI组、替格瑞洛治疗组、替格瑞洛预处理组和替格瑞洛预处理+治疗组。除Sham组外,其他各组通过结扎左前降支冠状动脉建立AMI模型。替格瑞洛治疗组在造模后给药,预处理组在造模前给药,预处理+治疗组在造模前后给药。比较各组左心室功能[左心室短轴缩短率(left ventricular fractional shortening,LVFS)、左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)和左心室收缩末期内径(left ventricular end-systolic diameter,LVESD)]、炎症标志物[白细胞介素-6(interleukin-6,IL-6)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)]、心脏指数以及血清心房钠尿肽(atrial natriuretic peptide,ANP)和脑钠尿肽(brain natriuretic peptide,BNP)mRNA表达水平。结果Sham组、替格瑞洛治疗组和替格瑞洛预处理+治疗组的LVFS[(42.12±5.20)%、(39.63±5.75)%和(41.72±6.31)%]高于AMI组的(33.98±5.21)%,差异有统计学意义(P<0.05),而LVEDD和LVESD则低于AMI组[(3.59±0.61)mm、(4.03±0.65)mm和(3.96±0.73)mm vs.(4.79±0.74)mm;(2.13±0.40)mm、(2.39±0.56)mm和(2.29±0.48)mm vs.(2.93±0.54)mm],差异均有统计学意义(F=3.894,3.471,P<0.05)。Sham组、替格瑞洛治疗组和替格瑞洛预处理+治疗组炎症因子IL-6和TNF-α水平低于AMI组[(110.50±25.34)pg/mL、(202.28±55.24)pg/mL和(189.49±43.31)pg/mL vs.(359.48±80.10)pg/mL;(24.59±6.95)pg/mL、(51.28±14.03)pg/mL和(47.49±11.16)pg/mL vs.(81.92±15.55)pg/mL],差异均有统计学意义(P<0.001)。Sham组、替格瑞洛治疗组和替格瑞洛预处理+治疗组的心脏指数分别为(4.90±0.84)、(5.44±0.90)和(5.31±0.84)低于AMI组的(6.39±1.29),差异有统计学意义(F=3.985,P<0.05)。替格瑞洛预处理组的心脏指数为(6.21±1.04),与AMI组比较,差异无统计学意义(P>0.05)。Sham组、替格瑞洛治疗组和替格瑞洛预处理+治疗组ANP的mRNA表达水平低于AMI组[(1.22±0.34)、(1.83±0.54)、(1.80±0.57)vs.(2.66±0.69);(1.08±0.24)、(1.48±0.56)、(1.38±0.49)vs.(2.45±0.75)],差异均有统计学意义(P<0.001)。结论替格瑞洛能够改善AMI后小鼠的左心室功能,并且增强心脏收缩功能,减小心室扩张程度,有效地减轻心肌炎症反应和降低心脏负荷。

Objective To investigate the effects of ticagrelor on left ventricular remodeling and cardiac function after acute myocardial infarction(AMI)in mice.Methods Eight-week-old male C57BL/6 mice were randomly divided into five groups:Sham group,AMI group,ticagrelor treatment group,ticagrelor pretreatment group,and ticagrelor pretreatment+treatment group.All groups,except for the Sham group,underwent left anterior descending coronary artery ligation to establish an AMI model.The ticagrelor treatment group received medication post-modeling,the pretreatment group pre-modeling,and the pretreatment+treatment group both preand post-modeling.Groups were compared for left ventricular function[left ventricular fractional shortening(LVFS),left ventricular end-diastolic diameter(LVEDD),and left ventricular end-systolic diameter(LVESD)],inflammatory markers[IL-6 and TNF-α],cardiac index,and mRNA expression levels of serum atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP).Results The left ventricular fractional shortening(LVFS)of the Sham group,the Ticagrelor treatment group,and the Ticagrelor pretreatment+treatment group[(42.12±5.20)%,(39.63±5.75)%,and(41.72±6.31)%]was higher than that of the AMI group[(33.98±5.21)%],with a statistically significant difference(P<0.05).In contrast,the left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were lower in the Sham group,the Ticagrelor treatment group,and the Ticagrelor pretreatment+treatment group[(3.59±0.61)mm,(4.03±0.65)mm,and(3.96±0.73)mm compared to(4.79±0.74)mm;(2.13±0.40)mm,(2.39±0.56)mm,and(2.29±0.48)mm compared to(2.93±0.54)mm],with statistically significant differences(P<0.05).The levels of inflammatory factors IL-6 and TNF-αin the Sham group,the Ticagrelor treatment group,and the Ticagrelor pretreatment+treatment group were lower than those in the AMI group[(110.50±25.34)pg/mL,(202.28±55.24)pg/mL,and(189.49±43.31)pg/mL vs.(359.48±80.10)pg/mL;(24.59±6.95)pg/mL,(51.28±14.03)pg/mL,and(47.49±11.16)pg/mL vs.(81.92±15.55)pg/mL],with statistically significant differences(P<0.001).The cardiac index of the Sham group,the Ticagrelor treatment group,and the Ticagrelor pretreatment+treatment group were(4.90±0.84),(5.44±0.90),and(5.31±0.84),respectively,which were lower than that of the AMI group(6.39±1.29),with a statistically significant difference(P<0.05).The cardiac index of the Ticagrelor pretreatment group was(6.21±1.04)points,with no statistically significant difference compared to the AMI group(P>0.05).The mRNA expression levels of ANP and BNP in the Sham group,the Ticagrelor treatment group,and the Ticagrelor pretreatment+treatment group were lower than those in the AMI group[(1.22±0.34),(1.83±0.54),and(1.80±0.57)compared to(2.66±0.69);(1.08±0.24),(1.48±0.56),and(1.38±0.49)compared to(2.45±0.75)],with statistically significant differences(P<0.001).Conclusion Ticagrelor can improve left ventricular function in mice after AMI,enhance cardiac contractile function,reduce effectively ventricular dilation,and alleviate myocarditis and cardiac load.