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白藜芦醇使人类颗粒细胞的膜电位去极化,并促进线粒体生物发生。

Resveratrol depolarizes the membrane potential in human granulosa cells and promotes mitochondrial biogenesis.

机构信息

Department of Chemistry, Biology and Biotechnologies, University of Perugia, Perugia, Italy.

Department of Chemistry, Biology and Biotechnologies, University of Perugia, Perugia, Italy; Department of Experimental Medicine, Perugia Medical School, University of Perugia, Perugia, Italy.

出版信息

Fertil Steril. 2021 Apr;115(4):1063-1073. doi: 10.1016/j.fertnstert.2020.08.016. Epub 2021 Jan 22.

DOI:10.1016/j.fertnstert.2020.08.016
PMID:33487442
Abstract

OBJECTIVE

To study the biological effects of resveratrol on the growth, electrophysiology, and mitochondrial function of human granulosa cells (h-GCs).

DESIGN

Preclinical study.

SETTING

Electrophysiology laboratory and in vitro fertilization unit.

PATIENT(S): This study included h-GCs from seven infertile women undergoing assisted reproductive techniques.

INTERVENTION(S): Human ovarian Granulosa Cell Tumor (GCT) cell line COV434 and h-GCs obtained after oocyte retrieval were cultured in the absence or presence of resveratrol.

MAIN OUTCOME MEASURE(S): Granulosa cells were evaluated for cell viability and mitochondrial activity. Electrophysiological recordings and evaluation of potassium current (IKur) and Ca concentration were also performed.

RESULT(S): Resveratrol induced mitochondrial activity in a bell-shaped, dose-effect-dependent manner. Specifically, resveratrol treatment (3 μM, 48 hours) increased ATP production and cell viability and promoted the induction of cellular differentiation. These biological changes were associated with mitochondrial biogenesis. Electrophysiological recordings showed that resveratrol reduced the functional expression of an ultra rapid activating, slow inactivating, delayed rectifier potassium current (IKur) that is associated with a plasma membrane depolarization and that promotes an increase in intracellular Ca CONCLUSION(S): The effects of resveratrol on potassium current and mitochondrial biogenesis in h-GCs could explain the beneficial effects of this polyphenol on the physiology of the female reproductive system. These findings suggest there are therapeutic implications of resveratrol in a clinical setting.

摘要

目的

研究白藜芦醇对人卵巢颗粒细胞(h-GCs)生长、电生理学和线粒体功能的生物学影响。

设计

临床前研究。

地点

电生理学实验室和体外受精单位。

患者

这项研究包括 7 名接受辅助生殖技术的不孕妇女的 h-GCs。

干预措施

人卵巢颗粒细胞瘤(GCT)细胞系 COV434 和卵母细胞回收后获得的 h-GCs 在不存在或存在白藜芦醇的情况下进行培养。

主要观察指标

评估颗粒细胞的细胞活力和线粒体活性。还进行了电生理记录和钾电流(IKur)和 Ca 浓度的评估。

结果

白藜芦醇以钟形、剂量依赖的方式诱导线粒体活性。具体来说,白藜芦醇处理(3 μM,48 小时)增加了 ATP 产生和细胞活力,并促进了细胞分化的诱导。这些生物学变化与线粒体生物发生有关。电生理记录显示,白藜芦醇降低了与质膜去极化相关的超快激活、缓慢失活、延迟整流钾电流(IKur)的功能表达,该电流促进细胞内 Ca 的增加。

结论

白藜芦醇对 h-GCs 钾电流和线粒体生物发生的影响可以解释这种多酚对女性生殖系统生理学的有益影响。这些发现表明,白藜芦醇在临床环境中有治疗意义。

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