【摘要】 目的研究雌激素对卵巢切除大鼠心脏雌激素受体(ER)α和β的调控及对血压、心率、心肌细胞心钠素(ANP)基因表达、合成和释放的影响。方法成年雌性Wistar大鼠随机分成5组假手术组,卵巢切除组和卵巢切除不同剂量17β-雌二醇组(80、800、8000ng·g-1·d-1)。测量大鼠收缩期血压(SBP)、心率;采用半定量RT-PCR和Western印迹方法,探讨不同剂量的17β-雌二醇对卵巢切除大鼠心脏ERα和ERβmRNA、ER蛋白质的表达调控及对ANPmRNA表达的影响;放射免疫方法测定血浆和心房组织ANP含量。结果超生理剂量的17β-雌二醇能降低卵巢切除大鼠SBP,减慢心率;成年雌性大鼠心脏ERαmRNA高于ERβmRNA的表达水平,而心房ERαmRNA表达又明显超过心室;卵巢切除减少心房ERαmRNA和蛋白质的表达,下调ANPmRNA,使心房组织和血浆ANP含量明显降低[(121±19)ng/mg组织vs(184±12)ng/mg组织,(196±21)ng/Lvs(288±36)ng/L,P<0.01];生理剂量17β-雌二醇能逆转上述改变。随剂量增加,17β-雌二醇的这种作用在一定程度上呈剂量依赖性关系。但卵巢切除和17β-雌二醇替代并不影响心脏ERβmRNA、心室ERαmRNA表达。结论超生理剂量雌激素可降低卵巢切除大鼠SBP,心率;ERα的高水平表达说明ERα是雌激素对心脏调控的优势受体;雌激素对心脏作用的主要靶部位是心房;雌激素促进心房肌细胞ANPmRNA的表达、合成和释放,通过受体依赖的ANP介导的通路发挥作用。更多还原

【Abstract】 ObjectiveTo investigate the effects of 17β-estradiol on regulation of estrogen receptor (ER) α and β, blood pressure, heart rate and expression, synthesis and release of atrial natriuretic peptide (ANP) in ovariectomized rat heart. MethodsAdult female Wistar rats were randomly divided into five groups: sham operated control, ovariectomized group and ovariectomized group treated with different concentrations of 17β-estradiol (three groups, 80, 800, 8000 ng·g-1·d-1). Systolic blood pressure (SBP) and heart rate were measured by the tail-cuff method with physiological recorder; changes in ERα and ERβ mRNA, ER protein, and ANP mRNA expressions were assessed in rat heart by RT-PCR and Western blot analysis; and plasma and tissue ANP concentrations were determined by radioimmunoassay. ResultsSBP and heart rate were significantly decreased in ovariectomized rats treated with superphysiological doses of 17β-estradiol; ERα mRNA in atria was dramatically higher than that in ventricle, ERα mRNA was significantly higher than ERβ mRNA in all heart chambers. Ovariectomy decreased atrial ERα mRNA, ERα protein, and ANP mRNA expressions, and reduced ANP concentration in plasma and tissue; treatment with approximately physiological dose of 17β-estradiol in ovariectomized rats reversed above changes; atrial ERα and ANP expressions, and atria and tissue ANP levels further increased to higher levels in a dose-dependent manner to some extent along with the increment of 17β-estradiol dosage. But ovariectomy and treatment with 17β-estradiol did not alter the heart ERβ mRNA and ventricular ERα expression. Conclusion17β-estradiol of superaphysiological doses decreases SBP and heart rate in ovariectomized rats; high ERα expression suggests that it functions as a predominant estrogenic receptor in adult heart, and as the atrial ERα is regulated by estrogen level, it may be inferred that estrogen mainly targets the atria and activates ANP via ERα-mediated channel to produce physiological effects.更多还原