van Eickels Martin, Patten Richard D, Aronovitz Mark J, Alsheikh-Ali Alawi, Gostyla Kim, Celestin Flore, Grohe Christian, Mendelsohn Michael E, Karas Richard H
Medizinsche Poliklinik II, University of Bonn, Bonn, Germany.
J Am Coll Cardiol. 2003 Jun 4;41(11):2084-92. doi: 10.1016/s0735-1097(03)00423-6.
This study was designed to examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after myocardial infarction (MI) in mice.
Observational and clinical studies suggest that the cardiovascular effects of hormone replacement therapy can differ depending on the patient population studied. No prospective studies have examined the effect of estrogen on outcomes following MI. We now examine the effects of estrogen replacement on infarct size, ventricular remodeling, and mortality after MI in mice.
Myocardial infarction was induced by left coronary artery ligation in ovariectomized female mice treated with 17-beta-estradiol (E2) or placebo. At either one day or six weeks after MI, hemodynamic function was assessed, animals were euthanized, and infarct size was determined.
17-beta-estradiol-treated mice had smaller infarcts than placebo-treated animals both one day (18% decrease; p < 0.01), and six weeks (14% decrease; p < 0.05) following MI. E2 reduced cardiomyocyte apoptosis as assessed by the terminal deoxynucleotidyl transferase uridine nucleotide end-labeling method (50% reduction, p < 0.05) and caspase 3 activation (33% reduction, p < 0.05). Despite having smaller infarcts, however, left ventricular mass increased more in the E2-treated animals (16% greater; p < 0.01). Left ventricular weight was positively correlated with infarct size in the estrogen-treated animals (R2 = 0.79, p = 0.0001). 17-beta-estradiol treatment also significantly increased mortality in the infarcted animals (relative risk of death = 2.4; 95% confidence interval 1.2 to 5.3).
Estrogen replacement therapy reduces infarct size and cardiomyocyte apoptosis in mice. However, estrogen increased post-MI ventricular remodeling and mortality. Further studies will be necessary to elucidate the mechanisms underlying the complex effects of estrogen observed in the present study.
本研究旨在探讨雌激素替代疗法对小鼠心肌梗死（MI）后梗死面积、心室重构及死亡率的影响。
观察性研究和临床研究表明，激素替代疗法的心血管效应可能因所研究的患者群体而异。尚无前瞻性研究探讨雌激素对心肌梗死后结局的影响。我们现在研究雌激素替代疗法对小鼠心肌梗死后梗死面积、心室重构及死亡率的影响。
通过结扎左冠状动脉，在接受17-β-雌二醇（E2）或安慰剂治疗的去卵巢雌性小鼠中诱导心肌梗死。在心肌梗死后1天或6周，评估血流动力学功能，对动物实施安乐死，并测定梗死面积。
在心肌梗死后1天（减少18%；p<0.01）和6周（减少14%；p<0.05），接受17-β-雌二醇治疗的小鼠梗死面积均小于接受安慰剂治疗的动物。通过末端脱氧核苷酸转移酶尿苷酸末端标记法评估，E2减少了心肌细胞凋亡（减少50%，p<0.05）以及半胱天冬酶3的激活（减少33%，p<0.05）。然而，尽管梗死面积较小，但接受E2治疗的动物左心室质量增加更多（增加16%；p<0.01）。在雌激素治疗的动物中，左心室重量与梗死面积呈正相关（R2 = 0.79，p = 0.0001）。17-β-雌二醇治疗还显著增加了梗死动物的死亡率（死亡相对风险 = 2.4；95%置信区间1.2至5.3）。
雌激素替代疗法可减少小鼠的梗死面积和心肌细胞凋亡。然而，雌激素增加了心肌梗死后的心室重构和死亡率。有必要进行进一步研究以阐明本研究中观察到的雌激素复杂效应的潜在机制。
