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苍附导痰汤通过 IGF-1-PI3K/Akt-Bax/Bcl-2 通路改善多囊卵巢综合征大鼠胰岛素抵抗及卵泡发育。

Cangfudaotan Decoction Alleviates Insulin Resistance and Improves Follicular Development in Rats with Polycystic Ovary Syndrome via IGF-1-PI3K/Akt-Bax/Bcl-2 Pathway.

机构信息

Department of Reproductive Medicine, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital, Hangzhou, 310003 Zhejiang, China.

出版信息

Mediators Inflamm. 2020 Nov 24;2020:8865647. doi: 10.1155/2020/8865647. eCollection 2020.

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder prevalent in females of reproductive age; insulin resistance (IR) is the major pathogenic driver. Pharmacology is a basic option for PCOS therapy; traditional Chinese medicine (TCM), as a significant part of complementary and alternative medicine, has a long history in the clinical management of PCOS. Cangfudaotan decoction (CFD) has been used clinically for gynaecological diseases especially PCOS. In this study, first, chemical components in CFD were clarified using UPLC-Q/TOF-MS analysis. Then, an animal model of PCOS was established, granular cells were also isolated from the rats with PCOS, and CFD was administrated at different dosages in PCOS rats and granular cells, to investigate the therapeutic effect and mechanisms of CFD for PCOS treatment. The result showed that CFD treatment is effective in PCOS rats and granulosa cells. CFD was able to improve IR, restore the serum hormone levels, inhibit the inflammatory cytokines in PCOS rat, and alleviate ovary morphological injury and apoptosis in PCOS rats. In granulosa cells of PCOS, the result showed that the cell viability was improved, and cell apoptosis was inhibited after CFD administration. Further experiments suggested that CDF improves IR, follicular development, cell apoptosis, and inflammatory microenvironment, and this was associated to the regulation of IGF-1-PI3K/Akt-Bax/Bcl-2 pathway-mediated gene expression. Given that CFD sufficiently suppresses insulin resistance and improves follicular development in this study, exploring these mechanisms might help to optimize the therapeutic treatment of CFD in PCOS patients.

摘要

多囊卵巢综合征(PCOS)是生殖年龄女性最常见的内分泌和代谢紊乱;胰岛素抵抗(IR)是主要的致病驱动因素。药理学是 PCOS 治疗的基本选择;作为补充和替代医学的重要组成部分,中药(TCM)在 PCOS 的临床管理中具有悠久的历史。苍附导痰汤(CFD)已在妇科疾病的临床中使用,特别是在 PCOS 中。在这项研究中,首先使用 UPLC-Q/TOF-MS 分析阐明了 CFD 中的化学成分。然后,建立了 PCOS 动物模型,还从 PCOS 大鼠中分离出颗粒细胞,并在 PCOS 大鼠和颗粒细胞中以不同剂量给予 CFD,以研究 CFD 治疗 PCOS 的治疗效果和机制。结果表明,CFD 治疗对 PCOS 大鼠和颗粒细胞有效。CFD 能够改善 IR,恢复血清激素水平,抑制 PCOS 大鼠中的炎性细胞因子,并减轻 PCOS 大鼠卵巢形态损伤和细胞凋亡。在 PCOS 的颗粒细胞中,结果表明 CFD 给药后细胞活力得到改善,细胞凋亡受到抑制。进一步的实验表明,CFD 通过调节 IGF-1-PI3K/Akt-Bax/Bcl-2 通路介导的基因表达来改善 IR、卵泡发育、细胞凋亡和炎症微环境。鉴于 CFD 在本研究中充分抑制了胰岛素抵抗并改善了卵泡发育,探索这些机制可能有助于优化 CFD 在 PCOS 患者中的治疗作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b37d/7707997/4ece78ffc86e/MI2020-8865647.001.jpg

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