摘要
目的:探究卡维地洛通过Janus激酶/信号转导和转录激活因子(JAK/STAT3)信号通路对急性心肌梗死(AMI)大鼠心肌损伤的保护作用。方法:45只SD大鼠随机分为Sham组、AMI组和AMI+卡维地洛组(n=15)。通过结扎建立AMI模型,卡维地洛灌胃干预。检测各组大鼠心电图和肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)等心肌酶;超声心动图检测心功能;HE染色和TUNEL染色检测组织损伤和心肌细胞凋亡;Western blot检测JAK和STAT蛋白磷酸化水平。结果:建模后第8天,AMI组出现明显的ST段抬高和Q波延长,AMI+卡维地洛组心电图恢复。AMI组大鼠左室射血分数(LVEF)、左室内压力最大变化率(±dp/dt max)水平均显著低于Sham组,AMI+卡维地洛组LVEF、±dp/dt max水平则显著高于AMI组,Sham组CKMB和LDH水平显著高于对照组,AMI+卡维地洛组CK-MB和LDH水平则显著低于AMI组;AMI组心肌细胞凋亡率显著高于Sham组,AMI+卡维地洛组凋亡率显著低于AMI组(P<0.05)。与Sham组比较,AMI组JAK和STAT3磷酸化水平显著降低(P<0.05),AMI+卡维地洛组JAK和STAT3磷酸化水平显著高于AMI组(P<0.05)。结论:卡维地洛通过促进PI3K/AKT信号通路的激活抑制AMI模型大鼠的心肌细胞凋亡,并发挥保护AMI心功能的作用。
Objective:To explore the protective effect of carvedilol on myocardial injury in rats with acute myocardial infarction(AMI)through JAK/STAT3 signaling pathway.Methods:Forty-five SD rats were randomly divided into the sham group,AMI group,and AMI+carvedilol group(n=15).An AMI model was established by ligation.Carvedilol was used for gavage intervention.The electrocardiogram and myocardial enzymes creatine kinase MB(CK-MB)and lactate dehydrogenase(LDH)were detected in each group of rats.Echocardiography was used to detect the cardiac function.HE staining and TUNEL staining were used to detect the tissue damage and cardiomyocyte apoptosis.Western blot was used to detect JAK and STAT protein phosphorylation.Results:On the 8th day after modeling,the ST segment elevation and Q-wave extension were apparent in AMI group.The ECG of AMI+carvedilol group recovered.The levels of LVEF and maximum change rate of left indoor pressure(±dp/dt max)in AMI group were significantly lower than those in the sham group(P<0.05).The levels of LVEF and±dp/dt max in AMI+carvedilol group were significantly higher than those in AMI group(P<0.05).CK-MB and LDH in the sham group were significantly higher than those in the control group(P<0.05).CK-MB and LDH in AMI+carvedilol group were significantly lower than those in AMI group(P<0.05).The apoptosis rate in AMI group(32.08%±5.62%)was significantly higher than that(3.95%±0.48%)in the sham group(P<0.05).The cardiomyocyte apoptosis rate(15.67%±4.01%)in AMI+carvedilol group was significantly lower than that in AMI group(P<0.05).Compared with those in the sham group,JAK and STAT3 phosphorylation levels were significantly reduced in AMI group(P<0.05).The levels of JAK and STAT3 phosphorylation in AMI+carvedilol group were significantly higher than those in AMI group(P<0.05).Conclusion:Resveratrol relieves myocardial apoptosis induced by AMI by inhibiting SIRT3/β-catenin/PPARγpathway,and reduces inflammation to improve myocardial function.
作者
孟燕
秦皓
马强
张军波
张波
庞宏刚
Meng Yan;Qin Hao;Ma Qiang;Zhang Junbo;Zhang Bo;Pang Honggang(Department of Peripheral Blood Vessels,the First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,China)
出处
《中国药师》
CAS
2020年第10期1890-1893,1904,共5页
China Pharmacist
基金
陕西省重点研发计划项目(编号:2017SF-254)。
