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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。
Objective To study the effects of estrogen on the regulation of estrogen receptor α and β and the effects on blood pressure, heart rate, ANP gene expression, synthesis and release in ovariectomized rats. Methods Adult female Wistar rats were randomly divided into 5 sham operation groups. The ovariectomized group and ovariectomized group received different doses of 17β-estradiol (80,800, 8000 ng · g-1 · d-1). The systolic blood pressure (SBP) and heart rate of rats were measured. Semiquantitative RT-PCR and Western blotting were used to investigate the effects of different doses of 17β-estradiol on ERα and ERβmRNA and ER protein expression in ovariectomized rats and on ANP mRNA Expression of the impact; radioimmunoassay method for determination of plasma and atrial tissue ANP content. RESULTS: 17β-Estradiol at a physiological dosage reduced the SBP of ovariectomized rats and decreased the heart rate. The expression of ERαmRNA in the heart of adult female rats was higher than that of ERβmRNA, while the expression of ERαmRNA in the atrium was significantly higher than that in the ventricle. Ovariectomy reduced atrial ERαmRNA and (121 ± 19) ng / mg tissue vs (184 ± 12) ng / mg tissue, (196 ± 21) ng / Lvs (288 ± 36) ng / mg tissue and ANP mRNA decreased significantly in atrial tissue and plasma. ng / L, P <0.01]; physiological dose of 17β-estradiol reversed the above changes. With the increase of dose, the effect of 17β-estradiol was to a certain extent in a dose-dependent manner. However, ovariectomy and 17β-estradiol replacement did not affect cardiac ERβ mRNA, ventricular ERα mRNA expression. Conclusion Hyperphysiological estrogen can reduce the SBP and heart rate in ovariectomized rats. The high expression of ERα indicates that ERα is the predominant receptor of estrogen on heart regulation. The main target site of estrogen on heart function is atrium. Estrogen promotes atrial The expression, synthesis and release of myocyte ANP mRNAs play a role through the receptor-dependent ANP-mediated pathway.