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Estradiol Valerate Enhances Cardiac Function via the Nrf2 Signaling Pathway to Protect Against Oxidative Stress by the Nrf2 Signaling Pathway in an Ovariectomized Rat Model
Current Pharmaceutical Design ( IF 2.6 ) Pub Date : 2021-11-30 , DOI: 10.2174/1381612827666210927162612
Xin Qian 1 , Jiao Wang 1 , Minghui Cai 1 , Haijuan Sun 1 , Han Xu 1 , Haixia Wen 1 , Hui Zhu 1
Affiliation  

Background: The increased risk of cardiovascular disease (CVD) in postmenopausal women and ovariectomized patients suggests that estrogen has a protective effect on cardiac function. Oxidative stress is the main cause of CVD, and the cellular defensive Nrf2 antioxidant pathway plays a protective role in various pathologies. However, the regulation of Nrf2 by estrogen has received little attention.

Objective: The present study aimed to investigate the role of Nrf2 in the effect of estrogen on cardiac function.

Methods: In the present study, female SD rats were divided into three groups as follows: sham operation (SHAM), bilateral ovariectomy (OVX) and bilateral ovariectomy with estradiol valerate (EV) supplementation (OVX+EV). Vaginal smears and E2 concentrations were used to confirm the success of the model. We compared cardiac morphology and function by echocardiography and HE staining. The levels of oxidative stress markers and antioxidant enzymes as well as protein expression of antioxidant genes were evaluated by Western blotting and immunohistochemistry.

Results: Our results showed that supplementation with estrogen restored the parameters to some extent. Left ventricular end diastolic diameter at diastolic (LVID;d) and left ventricular volume at diastolic (LV vol;d) increased but MV E wave/A wave (E/A) significantly decreased. The oxidative stress indicators (malondialdehyde) increased, and the antioxidant activity indicators, such as superoxide dismutase (SOD) and catalase (CAT), decreased. Further, the expression of most Nrf2 antioxidant pathway-related proteins in the heart decreased after ovariectomy.

Conclusion: The present study demonstrated that estrogen may protect cardiac function by regulating antioxidant capacity through the Nrf2 pathway.



中文翻译:

雌二醇戊酸酯通过 Nrf2 信号通路增强心脏功能,在去卵巢大鼠模型中通过 Nrf2 信号通路保护免受氧化应激

背景:绝经后妇女和卵巢切除患者心血管疾病 (CVD) 的风险增加表明雌激素对心脏功能具有保护作用。氧化应激是CVD的主要原因,细胞防御性Nrf2抗氧化途径在各种病理中发挥保护作用。然而,雌激素对 Nrf2 的调节作用却很少受到关注。

目的:本研究旨在探讨Nrf2在雌激素对心脏功能影响中的作用。

方法:在本研究中,雌性 SD 大鼠分为以下三组:假手术组(SHAM)、双侧卵巢切除术(OVX)和双侧卵巢切除术并补充戊酸雌二醇(EV)(OVX+EV)。阴道涂片和 E2 浓度用于确认模型的成功。我们通过超声心动图和 HE 染色比较了心脏形态和功能。通过蛋白质印迹和免疫组织化学评估氧化应激标志物和抗氧化酶的水平以及抗氧化基因的蛋白质表达。

结果:我们的结果表明,补充雌激素在一定程度上恢复了这些参数。舒张期左心室舒张末期直径 (LVID;d) 和舒张期左心室容积 (LV vol;d) 增加,但 MV E 波/A 波 (E/A) 显着降低。氧化应激指标(丙二醛)升高,超氧化物歧化酶(SOD)和过氧化氢酶(CAT)等抗氧化活性指标下降。此外,卵巢切除术后心脏中大多数 Nrf2 抗氧化途径相关蛋白的表达降低。

结论:本研究表明,雌激素可能通过 Nrf2 通路调节抗氧化能力来保护心脏功能。

更新日期:2021-11-24
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