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菊粉和二甲双胍通过抗炎和调节肠道微生物群改善多囊卵巢综合征小鼠的症状。

Inulin and metformin ameliorate polycystic ovary syndrome via anti-inflammation and modulating gut microbiota in mice.

机构信息

Department of Pathogenic Biology and Medical Immunology, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, Ningxia 750004, China.

The Center for Reproductive Medicine, General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, China.

出版信息

Endocr J. 2019 Oct 28;66(10):859-870. doi: 10.1507/endocrj.EJ18-0567. Epub 2019 Jul 3.

Abstract

Polycystic ovary syndrome (PCOS) represents an endocrine disorder, which is closely related with gut microbiota. Inulin, a kind of probiotics, has been proven to alleviate gut microbiota dysbiosis. Metformin, a biguanide agent, shows beneficial effects on chronic metabolic diseases. Our objective was to assess the effects and associated mechanisms of inulin and metforin on attenuation of PCOS in mice. Mice were divided into 4 groups: control group (CON), model group (MOD), inulin group (INU), metformin group (MET). The last three groups were fed 6 mg of dehydroepiandrosterone (DHEA) per 100 g body weight and 60% high-fat diet to generate mice model. After 21 days of intervention, mice were euthanized and associated indications were investigated. Body weight (BW) and testosterone (T) levels were significantly decreased, but estradiol (E2) levels were increased in INU or MET group, respectively. Ovary HE staining demonstrated that inulin or metformin ameliorated PCOS morphology. Inflammatory indicators from plasma and ovary including TNF-α, IL-6, and IL-17A were decreased in INU or MET group. Moreover, IL-10 in ovary of INU or MET group was increased. Sequencing and analysis of gut microbiota showed that compared to MOD group, Bifidobacterium was increased, but Proteobacteria, Helicobacter and Parasutterella were decreased in INU group. Helicobacter was decreased in MET group. Correlation analysis showed that gut microbiota was correlated with inflammatory factors. Our results revealed that inulin and metformin alleviated PCOS via anti-inflammation and modulating gut microbiota, which may contribute to potential clinical therapy for the disease.

摘要

多囊卵巢综合征(PCOS)代表一种内分泌紊乱,与肠道微生物群密切相关。菊粉是一种益生菌,已被证明可缓解肠道微生物群失调。二甲双胍是一种双胍类药物,对慢性代谢性疾病有有益的影响。我们的目的是评估菊粉和二甲双胍对减轻小鼠 PCOS 的作用及其相关机制。将小鼠分为 4 组:对照组(CON)、模型组(MOD)、菊粉组(INU)、二甲双胍组(MET)。后三组给予 100g 体重 6mg 脱氢表雄酮(DHEA)和 60%高脂肪饮食,以生成小鼠模型。干预 21 天后,处死小鼠并研究相关指标。INU 或 MET 组的体重(BW)和睾酮(T)水平显著降低,而雌二醇(E2)水平升高。卵巢 HE 染色表明,菊粉或二甲双胍改善了 PCOS 形态。INU 或 MET 组血浆和卵巢中的炎症指标 TNF-α、IL-6 和 IL-17A 降低。此外,INU 或 MET 组卵巢中的 IL-10 增加。肠道微生物群的测序和分析表明,与 MOD 组相比,INU 组双歧杆菌增加,而 Proteobacteria、Helicobacter 和 Parasutterella 减少。MET 组 Helicobacter 减少。相关性分析表明,肠道微生物群与炎症因子相关。我们的结果表明,菊粉和二甲双胍通过抗炎和调节肠道微生物群缓解 PCOS,这可能有助于该疾病的潜在临床治疗。

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