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白藜芦醇对体外子宫内膜异位症三维模型中人子宫内膜组织生长和血管生成的抑制作用。

Inhibitory effect of resveratrol on the growth and angiogenesis of human endometrial tissue in an In Vitro three-dimensional model of endometriosis.

机构信息

Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran.

出版信息

Reprod Biol. 2020 Dec;20(4):484-490. doi: 10.1016/j.repbio.2020.07.012. Epub 2020 Sep 28.

DOI:10.1016/j.repbio.2020.07.012
PMID:32896495
Abstract

Endometriosis is a chronic estrogen-dependent disorder and one of the most common causes of infertility in women. Resveratrol (RES) is a polyphenolic and phytoestrogenic compound with anti-oxidative, anti-inflammatory, anti-angiogenic, and anti-estrogenic properties. The aim of the present study was to investigate the effect of different concentrations of RES on human endometrial growth and angiogenesis in an in vitro three-dimensional (3D) model of endometriosis.Human endometrial tissues of endometriosis (endometriotic) and normal (endometrial) subjects (n = 9/groups) were biopsied in sterile conditions and cut into 1 × 2 mm pieces. Tissue fragments of each biopsy were given concentrations of 0 (control), 10, 50, 100 and 200 μM RES for 21 days in 3D culture condition using fibrin as an extracellular matrix. Scoring methods were used for tissue changes, including; cellular invasion, monolayer formation and angiogenesis. Nitric oxide (NO) was measured using Griess's reaction, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to evaluate the apoptotic gene expression.The mean of growth scores of endometriotic and endometrial tissue showed a significant dose dependent inhibition (P < 0.05). The levels of NO also significantly decreased in different groups. Apoptotic genes (P53, Bax, Bcl2 and caspase 3) and Sirt1 showed a significant increase in various concentrations of RES in both tissues (P < 0.05).RES exert dose- and time-dependent inhibitory effects on human endometrial tissue, and its higher doses suggested it as a natural supplement to inhibit the growth and treatment of endometriosis.

摘要

子宫内膜异位症是一种慢性雌激素依赖性疾病,也是女性不孕的最常见原因之一。白藜芦醇(RES)是一种多酚类和植物雌激素化合物,具有抗氧化、抗炎、抗血管生成和抗雌激素作用。本研究旨在探讨不同浓度 RES 对体外子宫内膜异位症(内异症)三维(3D)模型中人子宫内膜生长和血管生成的影响。在无菌条件下,从子宫内膜异位症(内异症)和正常(子宫内膜)患者(每组 n = 9)中活检人子宫内膜组织,并切成 1×2mm 小块。将每个活检的组织片段置于 3D 培养条件下,用纤维蛋白作为细胞外基质,给予 0(对照)、10、50、100 和 200μM RES 浓度 21 天。采用评分方法评估组织变化,包括细胞侵袭、单层形成和血管生成。使用 Griess 反应测定一氧化氮(NO),并采用定量实时聚合酶链反应(qRT-PCR)评估凋亡基因表达。内异症和子宫内膜组织的生长评分平均值呈明显的剂量依赖性抑制(P <0.05)。不同组的 NO 水平也明显降低。在两种组织中,凋亡基因(P53、Bax、Bcl2 和 caspase 3)和 Sirt1 在不同浓度 RES 下均显著增加(P <0.05)。RES 对人子宫内膜组织具有剂量和时间依赖性抑制作用,其高剂量可作为天然补充剂,抑制内异症的生长和治疗。

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