中药肝爽颗粒通过调节肠道微生物群减轻 CCl 诱导的肝纤维化。

Traditional Chinese Medicine Ganshuang Granules Attenuate CCl -Induced Hepatic Fibrosis by Modulating Gut Microbiota.

机构信息

Department of Integrated Traditional Chinese and Western Medicine, Tianjin Second People's Hospital, No.7, Sudi Nan Road, Naikai District, Tianjin, 300192, China.

Graduate School, Tianjin University of Traditional Chinese Medicine, No. 10, Poyanghu Road, Town West Area, Jinghai District, Tianjin, 301617, China.

出版信息

Chem Biodivers. 2021 Nov;18(11):e2100520. doi: 10.1002/cbdv.202100520. Epub 2021 Sep 29.

Abstract

Gut dysbiosis contributes to hepatic fibrosis. Emerging evidence revealed the major role of traditional Chinese medicine (TCM) in gut microbiota homeostasis. Here, we aimed to investigate the anti-fibrotic activity and underlying mechanism of ganshuang granules (GS), particularly regarding gut microbiota homeostasis. CCl -induced hepatic fibrosis models were allocated into 4 groups receiving normal saline (model), 1.0, 2.0, or 4.0 g/kg GS for 5 weeks. As result, GS treatment alleviated liver injury in CCl -induced hepatic fibrosis, presenting as decreases of the liver index, alanine aminotransferase, and aspartate transaminase. Histological staining and expression revealed that the enhanced oxidative stress, inflammatory and hepatic fibrosis in CCl -induced models were attenuated by GS. Immunohistochemical staining showed that tight junction-associated proteins in intestinal mucosa were up-regulated by GS. 16S rRNA sequencing showed that GS rebalanced the gut dysbiosis manifested as improving alpha and beta diversity of gut microbiota, reducing the ratio of Firmicutes to Bacteroidetes, and regulating the relative abundance of various bacteria. In summary, GS decreased the intestinal permeability and rebalanced the gut microbiota to reduce the oxidative stress and inflammation, eventually attenuating CCl -induced hepatic fibrosis.

摘要

肠道菌群失调可导致肝纤维化。新出现的证据表明,中药(TCM)在肠道微生物群落平衡中起着重要作用。本研究旨在探讨肝爽颗粒(GS)的抗纤维化作用及其作用机制,特别是对肠道微生物群落平衡的影响。采用 CCl4 诱导的肝纤维化模型,将其分为生理盐水(模型)组、1.0、2.0 和 4.0 g/kg GS 组,连续给药 5 周。结果表明,GS 治疗可减轻 CCl4 诱导的肝纤维化引起的肝损伤,表现为肝指数、丙氨酸转氨酶和天冬氨酸转氨酶降低。组织学染色和表达显示,GS 可减弱 CCl4 诱导模型中增强的氧化应激、炎症和肝纤维化。免疫组化染色显示,GS 可上调肠黏膜紧密连接相关蛋白。16S rRNA 测序结果显示,GS 可使肠道菌群失调得到再平衡,表现为改善肠道微生物群落的α多样性和β多样性,降低厚壁菌门与拟杆菌门的比例,并调节各种细菌的相对丰度。综上所述,GS 可降低肠道通透性,使肠道菌群再平衡,减少氧化应激和炎症,从而减轻 CCl4 诱导的肝纤维化。

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