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槲皮素通过改善炎症微环境降低多囊卵巢综合征大鼠模型的胰岛素抵抗。

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

机构信息

1 Department of Traditional Chinese Gynecology, Changhai Hospital, Second Military Medical University, Shanghai, China.

2 Department of Traditional Chinese Gynecology, Pudong TCM Hospital, Shanghai, China.

出版信息

Reprod Sci. 2017 May;24(5):682-690. doi: 10.1177/1933719116667218. Epub 2016 Sep 15.

DOI:10.1177/1933719116667218
PMID:27634381
Abstract

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

摘要

胰岛素抵抗(IR)是多囊卵巢综合征(PCOS)的临床特征。槲皮素来源于山楂等中草药,已被证明可有效治疗糖尿病的 IR。然而,槲皮素是否能降低 PCOS 的 IR 尚不清楚。本研究旨在观察槲皮素对 PCOS 大鼠模型 IR 的治疗作用,并探讨其潜在机制。通过皮下注射脱氢表雄酮建立 IR PCOS 大鼠模型。观察槲皮素治疗大鼠的体重、动情周期和卵巢形态。采用酶联免疫吸附试验分析血清炎性细胞因子。通过 Western blot、实时聚合酶链反应或免疫组织化学检测卵巢组织中炎症信号通路关键基因的表达。通过免疫荧光观察核因子 κB(NF-κB)的核转位。槲皮素治疗后胰岛素抵抗 PCOS 模型的动情周期恢复率为 58.33%。槲皮素显著降低了胰岛素、白细胞介素 1β、IL-6 和肿瘤坏死因子 α 的水平。槲皮素还显著减少了胰岛素抵抗 PCOS 大鼠模型中颗粒细胞 NF-κB 的核转位。该治疗抑制了卵巢组织中炎症相关基因的表达,包括烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基 p22phox、氧化型低密度脂蛋白和 Toll 样受体 4。槲皮素改善了 IR 并对 PCOS 大鼠具有良好的治疗效果。槲皮素的潜在作用机制可能涉及抑制 Toll 样受体/NF-κB 信号通路和改善 PCOS 大鼠卵巢组织的炎症微环境。

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