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小檗碱通过抑制 IKK/NF-κB、JNK 和 IRS-1/AKT 信号通路改善妊娠期糖尿病大鼠肝脏胰岛素抵抗。

Berberine Ameliorates Insulin Resistance by Inhibiting IKK/NF-κB, JNK, and IRS-1/AKT Signaling Pathway in Liver of Gestational Diabetes Mellitus Rats.

机构信息

Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

出版信息

Metab Syndr Relat Disord. 2022 Oct;20(8):480-488. doi: 10.1089/met.2022.0017. Epub 2022 Jul 21.

Abstract

Berberine is derived from rhizoma coptidis, a well-known Traditional Chinese herbal Medicine that has been found to be effective in the treatment of type 2 diabetes mellitus in recent years. The aim of the present study was to investigate the effects of berberine on a gestational diabetes mellitus (GDM) rat model and the related mechanisms. GDM was induced in Sprague-Dawley rats using a high-fat diet before and during pregnancy. Berberine (100 mg/kg/day) was administered from the 7th to 20th day of pregnancy. Insulin resistance (IR), glucose tolerance, and maternal, fetal, and placental weight were determined. Liver histopathological analysis, as well as analysis of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), inhibitor kappa B kinaseβ (IKKβ), nuclear factor kappa-B (NF-κB), c-Jun N-terminal kinase (JNK), insulin receptor substrate-1 (IRS-1), and protein kinase B (AKT), was performed at the end of pregnancy. Treatment of GDM rats with berberine markedly decreased IR, the number of dead and absorptive fetuses, maternal body weight gain, and fetal and placental weight compared with GDM without berberine. Furthermore, berberine decreased CRP and TNF-α levels, IKKβ expression, NF-κB P65 nuclear translocation, and changed the phosphorylation of JNK, IRS-1, and AKT in the liver of GDM rats. Berberine improved IR and maternal-fetal outcomes of GDM rats, possibly through modulation of IKK/NF-κB, JNK, and IRS-1/AKT signaling pathways in the liver. Therefore, berberine may be a potential GDM treatment.

摘要

小檗碱源自黄连,是一种传统中药,近年来已被证明对 2 型糖尿病有效。本研究旨在探讨小檗碱对妊娠期糖尿病(GDM)大鼠模型的影响及相关机制。通过在妊娠前和妊娠期间给予高脂肪饮食诱导 Sprague-Dawley 大鼠发生 GDM,从妊娠第 7 天至第 20 天给予小檗碱(100mg/kg/天)。测定胰岛素抵抗(IR)、葡萄糖耐量以及母鼠、胎鼠和胎盘的重量。在妊娠末期进行肝组织病理学分析以及 C 反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、抑制κB 激酶β(IKKβ)、核因子κB(NF-κB)、c-Jun N 末端激酶(JNK)、胰岛素受体底物-1(IRS-1)和蛋白激酶 B(AKT)分析。与未用小檗碱治疗的 GDM 大鼠相比,用小檗碱治疗的 GDM 大鼠的 IR、死胎和吸收胎数量、母鼠体重增加以及胎鼠和胎盘重量明显降低。此外,小檗碱降低了 CRP 和 TNF-α 水平、IKKβ 表达、NF-κB P65 核易位以及改变了 GDM 大鼠肝脏中 JNK、IRS-1 和 AKT 的磷酸化。小檗碱改善了 GDM 大鼠的 IR 和母婴结局,可能通过调节肝脏中的 IKK/NF-κB、JNK 和 IRS-1/AKT 信号通路。因此,小檗碱可能是一种潜在的 GDM 治疗药物。

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