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隐丹参酮通过调节 HMGB1/TLR4/NF-κB 信号通路缓解多囊卵巢综合征大鼠的症状。

Cryptotanshinone alleviates polycystic ovary syndrome in rats by regulating the HMGB1/TLR4/NF‑κB signaling pathway.

机构信息

Department of Gynecology, Shanghai University of Traditional Chinese Medicine, Shanghai Traditional Chinese Medicine Hospital, Shanghai 200071, P.R. China.

Department of Chinese and Western Medicine, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200011, P.R. China.

出版信息

Mol Med Rep. 2020 Nov;22(5):3851-3861. doi: 10.3892/mmr.2020.11469. Epub 2020 Aug 28.

Abstract

Cryptotanshinone (CRY) has been demonstrated to reverse reproductive disorders. However, whether CRY is effective in the treatment of polycystic ovary syndrome (PCOS) remains unknown. The aim of the present study was to evaluate the therapeutic potential of CRY in PCOS. A rat model of PCOS was established by daily injection of human chorionic gonadotropin and insulin for 22 days. Total body weight and ovarian weight, as well as the levels of luteinizing hormone (LH) and the LH to follicle‑stimulating hormone (FSH) ratio (LH/FSH) significantly increased in rats with PCOS, compared with controls. Moreover, the levels of testosterone (T), tumor necrosis factor (TNF)‑α and high‑mobility group box 1 protein (HMGB1) also increased. However, CRY treatment attenuated the increase in body weight, ovarian weight, LH, LH/FSH ratio, T, TNF‑α and HMGB1 levels, compared with the PCOS group. Treatment with CRY also reduced NF‑κB/p65, HMGB1 and toll‑like receptor (TLR)4 mRNA and protein expression levels in the ovarian tissue and granulosa cells, both in vitro and in vivo. Thus, CRY significantly mitigated the changes in body weight, ovary weight, hormone levels and inflammatory factor levels observed in rats with PCOS. Thus, CRY protects against PCOS‑induced damage of ovarian tissue, possibly through a regulatory pathway involving HMGB1, TLR4 and NF‑κB.

摘要

隐丹参酮(CRY)已被证明可逆转生殖障碍。然而,CRY 是否对多囊卵巢综合征(PCOS)有效尚不清楚。本研究旨在评估 CRY 在 PCOS 中的治疗潜力。通过每日注射人绒毛膜促性腺激素和胰岛素 22 天建立 PCOS 大鼠模型。与对照组相比,PCOS 大鼠的总体重和卵巢重量以及黄体生成素(LH)和黄体生成素与卵泡刺激素(FSH)比值(LH/FSH)水平显著升高。此外,睾酮(T)、肿瘤坏死因子(TNF)-α 和高迁移率族蛋白 B1(HMGB1)水平也升高。然而,与 PCOS 组相比,CRY 治疗可减弱体重、卵巢重量、LH、LH/FSH 比值、T、TNF-α 和 HMGB1 水平的升高。CRY 治疗还降低了卵巢组织和颗粒细胞中 NF-κB/p65、HMGB1 和 Toll 样受体 4(TLR4)mRNA 和蛋白表达水平,无论是在体外还是体内。因此,CRY 显著减轻了 PCOS 大鼠体重、卵巢重量、激素水平和炎症因子水平的变化。因此,CRY 可通过涉及 HMGB1、TLR4 和 NF-κB 的调节途径来保护卵巢组织免受 PCOS 引起的损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b70/7533513/b4bedfaad894/MMR-22-05-3851-g00.jpg

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