Estrogen receptor ERα plays a major role in ethanol-evoked myocardial oxidative stress and dysfunction in conscious female rats.
Estrogen receptor ERα plays a major role in ethanol-evoked myocardial oxidative stress and dysfunction in conscious female rats.
复制标题
雌激素受体 ERα 在清醒雌性大鼠乙醇引起的心肌氧化应激和功能障碍中起主要作用。
DOI：
10.1016/j.alcohol.2015.11.002
复制
发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Abdel-Rahman,AbdelA
中科院分区：
文献类型：
--
作者：
Yao,Fanrong;Abdel-Rahman,AbdelA
我们以前的研究表明，乙醇引起雌激素（E2）依赖性心肌氧化应激和功能障碍。在本研究中，我们验证了E2信号通过雌激素受体（ER），ERα，介导酒精对心肌的有害作用的假设。为了实现这一目标，处于发情前期（最高内源性E2水平）的清醒雌性大鼠接受选择性ER拮抗剂（200 μg/kg;静脉内[i. v.]）对于ERα（MPP）、ERβ（PHTPP）或GPER（G15）或生理盐水，在乙醇（1 g/kg; i. v.）或盐水注入。阻断ERα可有效地消除乙醇引起的心肌功能障碍和低血压，而阻断ERβ对乙醇引起的心肌收缩反应影响不大，但可延迟减轻乙醇引起的左室发展压力和左室压力上升速率的降低。GPER阻断引起乙醇的所有心血管效应的延迟衰减。所有这三种拮抗剂减弱了乙醇诱发的心肌过氧化氢酶和ALDH 2活性，Akt，ERK 1/2，p38，eNOS和nNOS磷酸化的增加，除了缺乏PHTPP对p38的影响。最后，所有三种ER拮抗剂都减弱了乙醇诱发的心肌ROS升高，但这种作用在ERα阻断剂中最为显著。结论：ERα在乙醇引起的E2依赖性心肌氧化应激和功能障碍中起重要作用，并可能作为改善E2依赖性心肌氧化应激和功能障碍的分子靶点。
Our previous studies showed that ethanol elicited estrogen (E2)-dependent myocardial oxidative stress and dysfunction. In the present study we tested the hypothesis that E2signaling via the estrogen receptor (ER), ERα, mediates this myocardial detrimental effect of alcohol. To achieve this goal, conscious female rats in proestrus phase (highest endogenous E2level) received a selective ER antagonist (200 μg/kg; intra-venous [i.v.]) for ERα (MPP), ERβ (PHTPP) or GPER (G15) or saline 30 min before ethanol (1 g/kg; i.v.) or saline infusion. ERα blockade virtually abrogated ethanol-evoked myocardial dysfunction and hypotension, while ERβ blockade had little effect on the hypotensive response, but caused delayed attenuation of the ethanol-evoked reductions in left ventricular developed pressure and the rate of left ventricle pressure rise. GPER blockade caused delayed attenuation of all cardiovascular effects of ethanol. All three antagonists attenuated the ethanol-evoked increases in myocardial catalase and ALDH2 activities, Akt, ERK1/2, p38, eNOS, and nNOS phosphorylation, except for a lack of effect of PHTPP on p38. Finally, all three ER antagonists attenuated ethanol-evoked elevation in myocardial ROS, but this effect was most notable with ERα blockade. In conclusion, ERα plays a greater role in, and might serve as a molecular target for ameliorating, the E2-dependent myocardial oxidative stress and dysfunction caused by ethanol.