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雌激素是女性体内主要的类固醇性激素。对于心肌缺血性伤害,切除卵巢的成年雌性大鼠在β-肾上腺素受体激动时,比正常雌性大鼠呈现更严重的心肌损伤;而去卵巢后的雌激素替补组大鼠对β-肾上腺素受体激动时心肌缺血性伤害的反应则又回复到正常雌性大鼠水平,这为雌激素对抗缺血性伤害的心脏保护作用提供了证据。雌激素的这种保护作用是通过下调β1-肾上腺素受体的表达来实现的。也有研究证明,雌激素能抑制蛋白激酶A(protein kinase A,PKA)的表达和活性,PKA是Gs蛋白/腺苷酸环化酶(adenylyl cyclase,AC)/cAMP/PKA通路的第二信使,而该通路最终影响心肌的收缩功能。有初步证据表明雌激素还能抑制β1-肾上腺素受体通路下游的另一种第二信使钙调蛋白激酶II-δc(Ca2+/calmodulin kinase II-δc,CaMKII-δc)的活性,而CaMKII-δc参与PKA非依赖性的细胞凋亡。即时给予生理浓度雌激素可不通过雌激素受体而直接抑制心肌β1-肾上腺素受体并减弱Ca2+内流。此外,脑研究也显示雌激素能抑制负责调节动脉血压脑区的β1-肾上腺素受体活性。因此,雌激素和β1-肾上腺素受体之间的相互作用及其信号通路十分复杂。雌激素不仅主导性别决定,在机体其它功能例如心脏保护方面也具有重要作用。
Estrogen is the main steroid hormone in women. For myocardial ischemic injury, adult ovariectomized female rats exhibit more severe myocardial damage than normal female rats when β-adrenergic agonists are excited; while the ovariectomized estrogen replacement rats respond to β- The response of myocardial ischemic injury to adrenergic receptor agonism returned to that of normal female rats, which provided evidence for the cardioprotective effect of estrogen against ischemic injury. This protective effect of estrogen is achieved by down-regulating β1-adrenergic receptor expression. Studies have also shown that estrogen can inhibit the expression and activity of protein kinase A (PKA), the second messenger of the Gs / ACAMP / PKA pathway, This pathway ultimately affects myocardial contractile function. There is preliminary evidence that estrogen also inhibits the activity of another second messenger CaMKII-δc (CaMKII-δc) downstream of the β1-adrenergic receptor pathway, whereas CaMKII- δc is involved in PKA-independent apoptosis. Immediate administration of physiological concentrations of estrogen directly inhibits β1-adrenergic receptors in the myocardium and attenuates Ca2 + influx without passing through the estrogen receptor. In addition, brain studies have also shown that estrogen inhibits β1-adrenergic receptor activity responsible for the regulation of arterial blood pressure in the brain. Therefore, the interaction between estrogen and β1-adrenergic receptors and their signaling pathways are complex. Estrogen not only dominates sex decisions but also plays an important role in other body functions such as cardioprotection.