G蛋白偶联雌激素受体（GPER）缺失通过氧化应激诱发心脏重塑
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G-protein coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress
背景与目的
卵巢激素缺失可通过氧化应激诱发心脏功能异常及心脏重塑。
方法与结果
使用卵巢切除大鼠模型，我们先前已经报道了G蛋白偶联雌激素受体(GPER)可以激发卵巢激素的心脏保护作用。与月龄及性别相匹配的雌性大鼠相比，我们发现九个月龄的雌性GPER敲除（GPER KO）大鼠，氧化应激和氧化损伤增多、谷胱甘肽/氧化型谷胱甘肽的比率(GSH/GSSG)减少、：4-羟基壬烯醛(HNE)、8-羟基2-脱氧鸟嘌呤核苷(8-oxo-DG)、与氧化应激相关的基因表达增多。雌性GPER敲除的大鼠表现为心脏重量和心脏胶原沉积、心室充盈压都增加，舒张早期二尖瓣环运动速度减少。使用甲磺酸（MitoQ）处理GPER KO大鼠8周，可显著减轻心功能紊乱。与无活性的焦磷酸硫胺素（dTPP）处理相比较，MitoQ可以减少8-羟基2-脱氧鸟嘌呤核苷(8-oxo-DG)浓度。PCR分析84列氧化应激及抗氧化防御基因，揭示了MitoQ可以抑制Nox4和Ptgs2表达增多、Ucp3和Gstk1的减少。
结 论
GPER的心脏保护作用包括抗氧化和靶向限制氧化应激可以有限的改善与卵巢激素缺失相关的心脏功能紊乱及心脏重塑。
原始文献摘要
Wang H ,Sun X ,Lin MS，etc. G-protein coupled estrogen receptor (GPER) deficiency induces cardiac remodeling through oxidative stress[J]. Transl Res,2018, (4),1-46.
Abstract：
Oxidative stress has been implicated in the unfavorable changes in cardiac function and remodeling that occur after ovarian estrogen loss. Using ovariectomized (OVX) rat models, we previously reported that the cardioprotective actions of estrogen are mediated by the G-protein coupled estrogen receptor (GPER). Here, in 9-month-old, female cardiomyocyte-specific GPER knockout (KO) mice vs. sex- and age-matched wild type (WT) mice, we found increased cardiac oxidative stress and oxidant damage, measured as a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), increased 4-hydroxynonenal (HNE) and 8-hydroxy-2′- deoxyguanosine (8-oxo-DG) staining, and increased expression of oxidative stress-related genes.GPER KO mice also displayed increased heart weight, cardiac collagen deposition, and Doppler- derived filling pressure (E/e′), and decreased percent fractional shortening and early mitral annular velocity (e′) compared to WT controls. Treatment of GPER KO mice for 8 weeks with MitoQ, a mitochondria-targeted antioxidant, significantly attenuated these measures of cardiac dysfunction, and MitoQ decreased 8-oxo-DG intensity compared to treatment with an inactive comparator compound dTPP (P < 0.05). A real-time PCR array analysis of 84 oxidative stress and antioxidant defense genes revealed that MitoQ attenuates the increase in Nox4 and Ptgs2 and Page 4 of 465 decrease in Ucp3 and Gstk1 seen in GPER KO mice. Our findings suggest that the cardioprotective effects of GPER include an antioxidant role and that targeted strategies to limit oxidative stress after early noncancerous surgical extirpation of ovaries or menopause may help limit alterations in cardiac structure and function related to estrogen loss.
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