Smith P J, Ornatsky O, Stewart D J, Picard P, Dawood F, Wen W H, Liu P P, Webb D J, Monge J C
Terrence Donnelly Heart Centre, Division of Cardiology, St. Michael's Hospital, University of Toronto, Toronto, Canada.
Circulation. 2000 Dec 12;102(24):2983-9. doi: 10.1161/01.cir.102.24.2983.
Estrogen may increase the long-term survival of women who have suffered from a myocardial infarction (MI). We examined the acute and chronic influence of estrogen on MI in the rat left coronary artery ligation model.
Female Sprague-Dawley rats (10 to 12 weeks, n=93), divided into 3 groups (rats with intact ovaries, ovariectomized rats administered 17beta-estradiol [17beta-E(2)] replacement, and ovariectomized rats administered placebo 2 weeks before MI), were randomized to left coronary artery ligation (n=66) or sham-operated (n=27) groups. Ten to 11 weeks after MI, rats were randomly assigned to either (1) assessment of left ventricular (LV) function and morphometric analysis or (2) measurement of cardiopulmonary mRNA expression of preproendothelin-1 and endothelin A and B receptors. Acutely, estrogen was associated with a trend toward increased mortality. Infarct size was increased in the 17beta-E(2) group compared with the placebo group (42+/-2% versus 26+/-3%, respectively; P:=0.01). Chronically, wall tension was normalized through a reduction in LV cavity size with estrogen treatment (419+/-41 mm Hg/mm for 17beta-E(2) versus 946+/-300 mm Hg/mm for placebo, P:=0.039). In the LV, there was a 2.5-fold increase in endothelin B mRNA expression after MI in placebo-treated rats (P:=0.004 versus sham-operated rats) that was prevented in the 17beta-E(2) group (P:=NS versus sham-operated rats).
These results suggest that estrogen is detrimental at the time of MI or early post-MI period, resulting in an increased size of infarct or infarct expansion, but chronically, it can normalize wall tension and inhibit LV dilatation, which may in turn lead to increased long-term survival. Regulation of the endothelin system, particularly the expression of the endothelin B receptor, may contribute to these estrogenic effects.
雌激素可能会提高心肌梗死（MI）女性患者的长期生存率。我们在大鼠左冠状动脉结扎模型中研究了雌激素对MI的急性和慢性影响。
将雌性Sprague-Dawley大鼠（10至12周龄，n = 93）分为3组（卵巢完整的大鼠、接受17β-雌二醇[17β-E₂]替代治疗的去卵巢大鼠、在MI前2周接受安慰剂治疗的去卵巢大鼠），随机分为左冠状动脉结扎组（n = 66）或假手术组（n = 27）。MI后10至11周，将大鼠随机分为两组，一组进行左心室（LV）功能评估和形态计量分析，另一组测量前内皮素-1以及内皮素A和B受体的心肺mRNA表达。急性情况下，雌激素与死亡率增加趋势相关。与安慰剂组相比，17β-E₂组的梗死面积增加（分别为42±2%和26±3%；P = 0.01）。慢性情况下，雌激素治疗通过减小LV腔大小使壁张力恢复正常（17β-E₂组为419±41 mmHg/mm，安慰剂组为946±300 mmHg/mm，P = 0.039）。在LV中，安慰剂治疗的大鼠MI后内皮素B mRNA表达增加2.5倍（与假手术组相比，P = 0.004），而在17β-E₂组中这种增加被阻止（与假手术组相比，P =无显著性差异）。
这些结果表明，雌激素在MI时或MI后早期是有害的，会导致梗死面积增加或梗死扩展，但长期来看，它可以使壁张力恢复正常并抑制LV扩张，这反过来可能导致长期生存率提高。内皮素系统的调节，特别是内皮素B受体的表达，可能有助于这些雌激素效应。
