Sang Li-Li, Zhou Chun-Le, Fu Lu, Chong Jing-Min, Zhang Lin, Cao Xian-Cun, Sun Hong
Department of Physiology, Xuzhou Medical College, Xuzhou 221004, China.
Sheng Li Xue Bao. 2014 Oct 25;66(5):583-8.
The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G α protein (Gαs)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17β-estradiol given group (OVX+E₂), OVX and isoprenaline injected group (OVX+ISO), OVX and 17β-estradiol, isoprenaline injected group (OVX+E₂+ISO). Rats were ovariectomized, and two weeks later, OVX+E₂group was injected with E₂, OVX+ISO group was injected with ISO, OVX+E₂+ISO group was injected with E₂and ISO. Another four weeks later, the hemodynamic parameters were monitored by carotid artery intubation: left ventricular systolic pressure (LVSP), left ventricular end-diastolic pressure (LVEDP), maximal differentials of left ventricular developed pressure (+dp/dt(max)), and minimal differentials of left ventricular developed pressure (-dp/dt(max)). Brain natriuretic peptide (BNP) and cAMP concentration in plasma were determined; Gα(s) protein expression in myocardium was determined. The results showed that the hemodynamic parameters, the concentration of BNP and cAMP in plasma had no significant changes after ovariectomy compared with sham group. But after isoprenaline injection in ovariectomized rats, LVSP and +dp/dt(max) declined (P < 0.01), LVEDP and -dp/dt(max) elevated (P < 0.01); plasma BNP concentration increased (P < 0.01); plasma cAMP concentration decreased (P < 0.01), compared with OVX group. Further estrogen supplements improved the heart function treated by isoprenaline: LVSP and +dp/dt(max) elevated (P < 0.01), LVEDP and -dp/dtmax declined (P < 0.05, P < 0.01); the plasma BNP concentration decreased (P < 0.01); the plasma cAMP concentration increased (P < 0.01). Estrogen had no significant influence on Gαs protein expression. The results suggest that estrogen can alleviate myocardial injury and regulate cardiac function disorder by increasing cAMP level, finally improved the excessive suppression of myocardium.
本研究旨在探讨雌激素通过调节刺激腺苷酸环化酶Gα蛋白（Gαs）-环磷酸腺苷（cAMP）信号通路来调控心脏功能紊乱的机制。成年雌性大鼠随机分为五组：假手术组、去卵巢组（OVX）、去卵巢并给予17β-雌二醇组（OVX+E₂）、去卵巢并注射异丙肾上腺素组（OVX+ISO）、去卵巢并注射17β-雌二醇及异丙肾上腺素组（OVX+E₂+ISO）。对大鼠进行去卵巢手术，两周后，OVX+E₂组注射E₂，OVX+ISO组注射ISO，OVX+E₂+ISO组注射E₂和ISO。再过四周后，通过颈动脉插管监测血流动力学参数：左心室收缩压（LVSP）、左心室舒张末期压力（LVEDP）、左心室压力最大上升速率（+dp/dt(max)）和左心室压力最大下降速率（-dp/dt(max)）。测定血浆中脑钠肽（BNP）和cAMP浓度；测定心肌中Gα(s)蛋白表达。结果显示，与假手术组相比，去卵巢后血流动力学参数、血浆中BNP和cAMP浓度无显著变化。但去卵巢大鼠注射异丙肾上腺素后，与OVX组相比，LVSP和+dp/dt(max)下降（P<0.01），LVEDP和-dp/dt(max)升高（P<0.01）；血浆BNP浓度升高（P<0.01）；血浆cAMP浓度降低（P<0.01）。进一步补充雌激素改善了异丙肾上腺素处理后的心脏功能：LVSP和+dp/dt(max)升高（P<0.01），LVEDP和-dp/dtmax下降（P<0.05，P<0.01）；血浆BNP浓度降低（P<0.01）；血浆cAMP浓度升高（P<0.01）。雌激素对Gαs蛋白表达无显著影响。结果表明，雌激素可通过提高cAMP水平减轻心肌损伤并调控心脏功能紊乱，最终改善心肌的过度抑制。
