Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Department of Gynecology and Obstetrics, School of Medicine, Tehran University of Medical Science, Tehran, Iran.
Am J Reprod Immunol. 2020 Jan;83(1):e13186. doi: 10.1111/aji.13186. Epub 2019 Nov 3.
Polycystic ovary syndrome (PCOS) is associated with endoplasmic reticulum (ER) stress and pro-inflammatory condition. The aim of the present study was to evaluate the effect of resveratrol treatment on pro-inflammatory and ER stress markers in patients with PCOS.
Cumulus cells were obtained from 40 patients with PCOS who were divided into two groups: placebo and resveratrol treatment (receiving 800 mg/d for 40 days) groups. Blood samples were obtained from all patients before and after the procedure to evaluate interleukin (IL)-6, IL-1β, IL-18, TNF-α, NF-κB, and C-reactive protein (CRP). Total RNA was extracted from cumulus cells, and cDNA was synthesized by reverse transcription. Expressions of five genes in ER stress response pathway (ATF4, ATF6, CHOP, GRP78, and XBP1s) were assessed with quantitative real-time PCR. Statistical analysis was performed with Student's t test.
After treatment with resveratrol, it was found that serum levels of IL-6, IL-1β, TNF-α, IL-18, NF-κB, and CRP decreased in the treatment group. In addition, gene expression results showed that the expression levels of ATF4 (P < .05) and ATF6 (P < .001) significantly increased in the resveratrol treatment group, while the expression levels of CHOP, GRP78, and XBP1 (P < .001 for all) significantly decreased.
Results demonstrated that resveratrol has anti-inflammatory effects through the suppression of NF-κB and NF-κB-regulated gene products. On the other hand, resveratrol can modulate ER stress in granulosa cells (GCs) by altering the expression of genes involved in unfolding protein response (UPR) process. Our findings suggest that ER stress is a potential therapeutic target for patients with PCOS.
多囊卵巢综合征(PCOS)与内质网(ER)应激和促炎状态有关。本研究旨在评估白藜芦醇治疗对 PCOS 患者促炎和 ER 应激标志物的影响。
从 40 名 PCOS 患者中获取卵丘细胞,将其分为两组:安慰剂组和白藜芦醇治疗组(每天接受 800mg,共 40 天)。所有患者在治疗前后均采集血样,以评估白细胞介素(IL)-6、IL-1β、IL-18、TNF-α、NF-κB 和 C 反应蛋白(CRP)。从卵丘细胞中提取总 RNA,通过逆转录合成 cDNA。采用实时定量 PCR 评估 ER 应激反应途径中 5 个基因(ATF4、ATF6、CHOP、GRP78 和 XBP1s)的表达。采用 Student's t 检验进行统计学分析。
白藜芦醇治疗后,治疗组血清中 IL-6、IL-1β、TNF-α、IL-18、NF-κB 和 CRP 水平降低。此外,基因表达结果显示,白藜芦醇治疗组 ATF4(P<.05)和 ATF6(P<.001)的表达水平显著增加,而 CHOP、GRP78 和 XBP1(P<.001)的表达水平显著降低。
结果表明,白藜芦醇通过抑制 NF-κB 和 NF-κB 调节的基因产物发挥抗炎作用。另一方面,白藜芦醇通过改变参与未折叠蛋白反应(UPR)过程的基因表达,调节颗粒细胞(GCs)中的 ER 应激。我们的研究结果表明,ER 应激是 PCOS 患者的一个潜在治疗靶点。