DSpace About DSpace Software 日本語

01 奈良県立医科大学 >
012 大学院 >
0122 学位請求論文 >
01221 博士論文(医学) >
2022年度 >

Please use this identifier to cite or link to this item: http://hdl.handle.net/10564/4091

Title: Rifaximin and lubiprostone mitigate liver fibrosis development by repairing gut barrier function in diet–induced rat steatohepatitis
Other Titles: リファキシミンとルビプロストンの併用は脂肪性肝炎ラットの腸管バリア機能を修復し肝線維化を抑制する
Authors: Enomoto, Masahide
Kaji, Kosuke
Nishimura, Norihisa
Fujimoto, Yuki
Murata, Koji
Takeda, Soichi
Tsuji, Yuki
Fujinaga, Yukihisa
Tanaka, Hiroaki
Kawaratani, Hideto
Namisaki, Tadashi
Akahane, Takemi
Yoshiji, Hitoshi
Keywords: Gut-liver axis
Non-alcoholic steatohepatitis
Issue Date: Oct-2022
Publisher: Elsevier
Citation: Digestive and liver disease Vol.54 No.10 p.1392-1402 (2022 Oct)
Abstract: Background: Although gut-derived lipopolysaccharide (LPS) affects the progression of non-alcoholic steatohepatitis (NASH) pathogenesis, few studies have focused on this relationship to develop treatments for NASH. Aims: To explore the effects of combination with rifaximin and lubiprostone on NASH liver fibrosis through the modulation of gut barrier function. Methods: To induce steatohepatitis, F344 rats were fed a choline-deficient l -amino acid-defined (CDAA) diet for 12 weeks and received oral administration of rifaximin and/or lubiprostone. Histological, molec- ular, and fecal microbial analyses were performed. Barrier function in Caco-2 cells were assessed by in vitro assays. Results: Combination rifaximin/lubiprostone treatment significantly suppressed macrophage expansion, proinflammatory responses, and liver fibrosis in CDAA-fed rats by blocking hepatic translocation of LPS and activation of toll-like receptor 4 signaling. Rifaximin and lubiprostone improved intestinal perme- ability via restoring tight junction proteins (TJPs) with the intestinal activation of pregnane X receptor and chloride channel-2, respectively. Moreover, this combination increased the abundance of Bacteroides, Lactobacillus, and Faecalibacterium as well as decreased that of Veillonella resulting in an increase of fecal short-chain fatty acids and a decrease of intestinal sialidase activity. Both agents also directly suppressed the LPS-induced barrier dysfunction and depletion of TJPs in Caco-2 cells. Conclusion: The combination of rifaximin and lubiprostone may provide a novel strategy for treating NASH-related fibrosis.
Description: 博士(医学)・甲第860号・令和5年3月15日
URI: http://hdl.handle.net/10564/4091
ISSN: 15908658
DOI: https://doi.org/10.1016/j.dld.2022.04.012
Academic Degrees and number: 24601甲第860号
Degree-granting date: 2023-03-15
Degree name: 博士(医学)
Degree-granting institutions: 奈良県立医科大学
Appears in Collections:2022年度

Files in This Item:

File Description SizeFormat
01甲860本文の要旨.pdf188.73 kBAdobe PDFView/Open
02甲860審査要旨.pdf210.01 kBAdobe PDFView/Open
03甲860本文.pdf844.83 kBAdobe PDFView/Open
04甲860Fig..pdf1.08 MBAdobe PDFView/Open

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


Valid XHTML 1.0! DSpace Software Copyright © 2002-2010  Duraspace - Feedback