Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis

Guizhi Fuling Wan, Chinese Herbal Medicine, Ameliorates Insulin Sensitivity in PCOS Model Rats With Insulin Resistance via Remodeling Intestinal Homeostasis
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桂枝茯苓丸通过重塑肠道稳态改善胰岛素抵抗多囊卵巢综合征模型大鼠的胰岛素敏感性

DOI:
10.3389/fendo.2020.00575
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发表时间:
2020-08
期刊:
Front. Endocrinol
影响因子:
--
通讯作者:
Hongqiu Zhu
Hongqiu Zhu
中科院分区:
其他
文献类型:
--
作者:
Ying Zhu;Yin Li;Min Liu;XiaoDan Hu;Hongqiu Zhu

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多囊卵巢综合征(PCOS)是育龄妇女常见的内分泌疾病,伴有生殖功能障碍和代谢紊乱。胃肠道微生物群通过介导胰岛素抵抗而参与多囊卵巢综合征的发病。桂枝涪陵丸可治疗多囊卵巢综合征合并胰岛素抵抗(PCOS-IR),但其作用机制尚不清楚。本研究旨在探讨桂枝涪陵丸的确切作用机制及其是否与调节肠道菌群结构有关。用来曲唑羧甲基纤维素钠(CMC-NA)溶液联合高脂乳剂诱导PCOS-IR大鼠模型,随机分为空白对照组(K)、模型对照组(M)、桂枝涪陵丸低剂量组(D)、桂枝涪陵丸中剂量组(Z)、桂枝涪陵丸高剂量组(G)和阳性药(Y)对照组。造模和治疗36天后,收集所有大鼠的血清和粪便样本进行随访分析。结果显示,与K组相比,M组睾酮和HOMA-IR升高,动情周期紊乱,卵巢多囊,表明PCOS-IR大鼠模型建立成功。与K组相比,M组肠道菌群改变(与K组相比,M组中变态杆菌的相对丰度显著降低,而乳杆菌、乳杆菌、瘤胃杆菌、反刍球菌科UCG-003的相对丰度显著增加)诱导炎症标志物的分泌。另一方面,桂枝涪陵丸可以减轻炎症,改善胰岛素抵抗:与M组相比,G组炎症减轻,空腹胰岛素减少,这与桂枝涪陵丸对肠道菌群的调节作用有关(G组与M组相比,别杆菌、反刍球菌科UCG-003、沙棘螺科UCG-008的相对丰度显著增加)。本研究证明桂枝涪陵丸改善多囊卵巢综合征患者的胰岛素抵抗,其机制可能与调节肠道菌群控制炎症有关。桂枝涪陵丸对PCOS-IR的治疗效果有一定的促进作用。
Polycystic ovary syndrome (PCOS) is a common endocrine disease with reproductive dysfunction and metabolic disorder in women of childbearing age. Gastrointestinal microbiome contributes to PCOS through mediating insulin resistance. Guizhi Fuling Wan, Chinese herbal medicine, can treat PCOS with insulin resistance (PCOS-IR), but the underlying mechanism is not clear. The aim of this study was to characterize the exact mechanism of Guizhi Fuling Wan action and whether it is related to the regulation of intestinal flora structure. We induced PCOS-IR rat model by means of letrozole sodium carboxymethyl cellulose (CMC-na) solution combined with high-fat emulsion administration and randomly divided it into blank control group (K), model control group (M), low dose of Guizhi Fuling Wan group (D), middle dose of Guizhi Fuling Wan group (Z), high dose of Guizhi Fuling Wan group (G) and positive drug (Metformin) control group (Y). After 36 days of modeling and treatment, serum and stool samples from all rats were collected for a follow-up analysis. The data display that, compared with K group, elevated testosterone and HOMA-IR, turbulent estrous cycles and polycystic ovaries in M group, indicating the PCOS-IR rat model is successfully established. Increased fasting insulin is associated with higher inflammation(plasma TNF-α, IL-6, and HS-CPR concentration were determined) in M group, and the altered intestinal flora (compared with the K group, in M group the relative abundance of Alloprevotella was decreased significantly, while the relative abundance of Lachnospiraceae UCG-008, Lachnospiraceae NK4A136, Lactobacillus, Ruminiclostridium 9, and Ruminococcaceae UCG-003 was increased significantly) induced the secretion of inflammatory markers. On the other hand, Guizhi Fuling Wan can alleviate inflammation, improve insulin resistence: Lower inflammation decreased fasting insulin can be seen in G group compared with M group, this effect is related to the regulating effect of Guizhi Fuling Wan on intestinal flora (in G group, the relative abundance of Alloprevotella, Ruminococcaceae UCG-003, and Lachnospiraceae UCG-008 was increased significantly, compared with M group). This research demonstrates Guizhi Fuling Wan improve insulin resistance in polycystic ovary syndrome with the underlying mechanism of regulating intestinal flora to control inflammation. It would be useful to promote the therapeutic effect of Guizhi Fuling Wan on PCOS-IR.
DOI: 10.3969/j.issn.1674-8115.2018.04.019
发表时间: 2018-04
期刊: Journal of Shanghai Jiaotong University
影响因子: --
作者:
Wang Yin-yu;Liu Ye;Huang He-feng
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