摘要
目的:本研究探讨N-乙酰半胱氨酸(N-acetylcysteine,NAC)在糖尿病性心肌病中独立于冠脉因素之外的抗心衰机制。方法:40只糖尿病小鼠建立心衰模型后随机分为两组,NAC组(NAC 100mg·kg^(-1)·d^(-1))20只,对照组(生理盐水100mg·kg^(-1)·d^(-1))20只。两组均4周后行超声心动图检查左室舒张末容积(LVEDV)、左室收缩末容积(LVESV)、左室射血分数(LVEF)、二尖瓣左室舒张早期最大血流速度/左室舒张晚期最大血流速度(E/A)、等容舒张时间(IVRT)和心输出量(CO),6周后应用原位末端缺口标记法(TUNEL)检测心肌细胞凋亡指数和Western Blot检测细胞外调节蛋白激酶(ERK)1/2蛋白表达水平。结果:与对照组比较,NAC组LVEF[(40.5±3.4)%比(36.9±3.2)%]、E/A[(1.5±0.1)比(1.4±0.1)]、CO[(10.3±0.6)ml/min比(9.9±0.5)ml/min]显著升高(P<0.05或<0.01);LVESV[(23.1±1.3)μl比(24.7±1.5)μl]、凋亡指数[(31.2±0.5)%比(45.1±0.9)%]、ERK1/2蛋白表达[(2.2±0.2)比(3.9±0.1)]显著降低(P均<0.001)。结论:NAC通过ERK1/2通路减少心肌细胞凋亡从而发挥抗心衰作用。
Objective:To investigate the anti-heart failure mechanism of N-acetylcysteine(NAC)in diabetic cardiomyopathy independent from coronary artery factors.Methods:A total of 40 diabetic mice after heart failure model construction were randomly divided into two groups,NAC group(n=20,NAC 100mg·kg^(-1)·d^(-1))and control group(n=20,Saline 100 mg·kg^(-1)·d^(-1)).Echocardiography was performed to detect left ventricular end-diastolic volume(LVEDV),left ventricular end-systolic volume(LVESV),left ventricular ejection fraction(LVEF),mitral left ventricular early-diastolic peak flow velocity/left ventricular late-diastolic peak flow velocity(E/A),isovolumic relaxation time(IVRT)and cardiac output(CO)after 4 weeks.Terminal uridine nick-end labeling(TUNEL)was performed to detect apoptosis index,and Western Blot was performed to detect the expression of extracellular regulated protein kinases(ERK)1/2 after 6 weeks in two groups.Results:Compared to those in control group,mice in NAC group had significant higher LVEF[(40.5±3.4)%vs.(36.9±3.2)%],E/A[(1.5±0.1)vs.(1.4±0.1)]and CO[(10.3±0.6)ml/min vs.(9.9±0.5)ml/min](P<0.05 or<0.01);and significant lower LVESV[(23.1±1.3)μl vs.(24.7±1.5)μl],apoptosis index[(31.2±0.5)%vs.(45.1±0.9)%]and the expression of ERK1/2[(2.2±0.2)vs.(3.9±0.1)](P<0.001 all).Conclusion:NAC exerts anti-heart failure effect by attenuating apoptosis of cardiomyocytes via regulating ERK1/2 pathway.
作者
季俭
黄亚红
卢英民
岳冬梅
郑晓辉
张金春
王朝霞
JI Jian;HUANG Ya-hong;LU Ying-min;YUE Dong-mei;ZHENG Xiao-hui;ZHANG Jin-chun;WANG Zhao-xia(Department of Cardiology,Chongming Hospital Affiliated to Shanghai University of Medicine&Health Sciences,Shanghai,202150,China)
出处
《心血管康复医学杂志》
2025年第4期543-547,共5页
Chinese Journal of Cardiovascular Rehabilitation Medicine
基金
上海市崇明区科学技术委员会“可持续发展科技创新行动计划”项目(CKY2021-16)。
关键词
心肌疾病
糖尿病
乙酰半胱氨酸
心力衰竭
Cardiomyopathies
Diabetes mellitus
Acetylcysteine
Heart failure
