Daikenchuto, a Kampo Medicine, Regulates Intestinal Fibrosis Associated with Decreasing Expression of Heat Shock Protein 47 and Collagen Content in a Rat Colitis Model

被引:1
|
作者
Inoue, Ken [1 ]
Naito, Yuji [1 ]
Takagi, Tomohisa [1 ]
Hayashi, Natsuko [1 ]
Hirai, Yasuko [1 ]
Mizushima, Katsura [1 ]
Horie, Ryusuke [1 ]
Fukumoto, Kohei [1 ]
Yamada, Shinya [1 ]
Harusato, Akihito [1 ]
Hirata, Ikuhiro [1 ]
Omatsu, Tatsushi [1 ]
Yoshida, Naohisa [1 ]
Uchiyama, Kazuhiko [1 ]
Ishikawa, Takeshi [1 ]
Handa, Osamu [1 ]
Konishi, Hideyuki [1 ]
Wakabayashi, Naoki [1 ]
Yagi, Nobuaki [1 ]
Ichikawa, Hiroshi [2 ]
Kokura, Satoshi [1 ]
Yoshikawa, Toshikazu [1 ]
机构
[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Mol Gastroenterol & Hepatol, Kamigyo Ku, Kyoto 6028566, Japan
[2] Doshisya Univ, Dept Med Life Syst, Kyoto 6100394, Japan
关键词
Daikenchuto; heat shock protein 47; myofibroblast; DAI-KENCHU-TO; IDIOPATHIC PULMONARY-FIBROSIS; HERBAL MEDICINE; CROHNS-DISEASE; BINDING HEAT-SHOCK-PROTEIN-47; CHRONIC INFLAMMATION; LIVER FIBROSIS; SULFONIC-ACID; TGF-BETA; HSP47;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Heat shock protein (HSP) 47 may play an important role in the pathogenesis of intestinal fibrosis. Daikenchuto (DKT), a traditional Japanese herbal (Kampo) medicine, has been reported to ameliorate intestinal inflammation. The aims of this study were to determine time-course profiles of several parameters of fibrosis in a rat model, to confirm the HSP47-expressing cells in the colon, and finally to evaluate DKT's effects on intestinal fibrosis. Colitis was induced in male Wistar rats weighing 200g using an enema of trinitrobenzene sulfonic acid (TNBS). HSP47 localization was determined by immunohistochemistry. Colonic inflammation and fibrosis were assessed by macroscopic, histological, morphometric, and immunohistochemical analyses. Colonic mRNA expression of transforming growth factor beta 1 (TGF-beta 1), HSP47, and collagen type I were assessed by real time-polymerase chain reaction (PCR). DKT was administered orally once a day from 8 to 14d after TNBS administration. The colon was removed on the 15th day. HSP47 immunoreactivity was coexpressed with alpha-smooth muscle actin-positive cells located in the subepithelial space. Intracolonic administration of TNBS resulted in grossly visible ulcers. Colonic inflammation persisted for 6 weeks, and fibrosis persisted for 4 weeks after cessation of TNBS treatment. The expression levels of mRNA and proteins for TGF-beta 1 HSP47, and collagen I were elevated in colonic mucosa treated with TNBS. These fibrosis markers indicated that DKT treatment significantly inhibited TNBS-induced fibrosis. These findings suggest that DKT reduces intestinal fibrosis associated with decreasing expression of HSP47 and collagen content in the intestine.
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页码:1659 / 1665
页数:7
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