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替格瑞洛对AMI后小鼠左心室重构及心功能的影响

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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。
Effects of Ticagrelor on Left Ventricular Remodeling and Cardiac Function After AMI in Mice
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 pre-and 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-α in 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/m L 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.

ticagreloracute myocardial infarctionleft ventricular remodelingcardiac functioninflammatory responsecardioprotection

王强生、李莉

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北京核工业医院全科病房,北京 100045

北京核 工业医院医院办公室,北京 100045

替格瑞洛 急性心肌梗死 左心室重构 心功能 炎症反应 心脏保护

2024

中国卫生标准管理
《中国卫生标准管理》杂志社

中国卫生标准管理

影响因子:1.374
ISSN:1674-9316
年,卷(期):2024.15(15)