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高浓度胰岛素通过增加细胞外高迁移率族蛋白B1(HMGB1)促进原代培养的大鼠卵巢颗粒细胞凋亡。

High concentration of insulin promotes apoptosis of primary cultured rat ovarian granulosa cells via its increase in extracellular HMGB1.

作者信息

Ni Xiao-Rong, Sun Zhou-Jun, Hu Guo-Hua, Wang Rong-Hui

机构信息

Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China

Gynecology Department, Shanghai Traditional Chinese Medicine Hospital, Shanghai, People's Republic of China.

出版信息

Reprod Sci. 2015 Mar;22(3):271-7. doi: 10.1177/1933719114549852. Epub 2014 Sep 16.

DOI:10.1177/1933719114549852
PMID:25228632
Abstract

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. Insulin resistance/hyperinsulinemia is a prevalent finding in women with PCOS, which indicates that insulin resistance/hyperinsulinemia may be an important player in the pathogenesis of the PCOS. However, the underlying mechanism of insulin resistance/hyperinsulinemia on the pathogenesis of the PCOS remains elusive. In this study, we found an increased high-mobility group box 1 (HMGB1) in the serum from women with PCOS having insulin resistance/hyperinsulinemia. Furthermore, we discovered that high concentration of insulin, which mimics insulin resistance model, promoted apoptosis in primary cultured rat ovarian granulosa cells (GCs) via its effect on the increase in extracellular HMGB1. Our data presented the first evidence that increased HMGB1 induced by insulin resistance/hyperinsulinemia promoted apoptosis of ovarian GCs, which provided new molecular basis for the PCOS pathogenesis.

摘要

多囊卵巢综合征(PCOS)是一种影响育龄女性的常见内分泌紊乱疾病。胰岛素抵抗/高胰岛素血症在PCOS女性中很常见,这表明胰岛素抵抗/高胰岛素血症可能是PCOS发病机制中的一个重要因素。然而,胰岛素抵抗/高胰岛素血症在PCOS发病机制中的潜在机制仍不清楚。在本研究中,我们发现患有胰岛素抵抗/高胰岛素血症的PCOS女性血清中高迁移率族蛋白B1(HMGB1)升高。此外,我们发现模拟胰岛素抵抗模型的高浓度胰岛素通过增加细胞外HMGB1促进原代培养的大鼠卵巢颗粒细胞(GCs)凋亡。我们的数据首次证明,胰岛素抵抗/高胰岛素血症诱导的HMGB1增加促进了卵巢GCs凋亡,这为PCOS发病机制提供了新的分子基础。

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