大建中汤对甲氨蝶呤诱导的急性小肠黏膜损伤模型的治疗作用及机制。
Therapeutic effect and mechanism of Daikenchuto in a model of methotrexate-induced acute small intestinal mucositis.
机构信息
Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Department of Surgery, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, Guangdong, China.
出版信息
PLoS One. 2023 Mar 30;18(3):e0283626. doi: 10.1371/journal.pone.0283626. eCollection 2023.
BACKGROUND
Daikenchuto (DKT) has positive therapeutic effects on improving various gastrointestinal disorders. The present study investigated whether or not DKT has a potential therapeutic effect on chemotherapy-induced acute small intestinal mucositis (CIM) in a rat model.
METHODS
Intraperitoneal injection of 10 mg/kg methotrexate (MTX) every 3 days for a total of 3 doses was used for induction of CIM in a rat model. The MTX and DKT-MTX groups were injected with MTX as above from the first day, and the DKT-MTX and DKT groups were administered 2.7% DKT via the diet at the same time. The rats were euthanized on day 15.
RESULTS
The DKT-MTX group showed an improvement in the body weight and conditions of gastrointestinal disorders as well as increased levels of diamine oxidase in plasma and in the small intestinal villi. The pathology results showed that small intestinal mucosal injury in the DKT-MTX group was less severe than that in the MTX group. Immunohistochemistry for myeloperoxidase and malondialdehyde and quantitative real-time polymerase chain reaction (RT-qPCR) for TGF-β1 and HIF-1α showed that DKT attenuated peroxidative damage. The crypts in the DKT-MTX group contained more Ki-67-positive cells than MTX group. The zonula occluden-1 and claudin-3 results showed that DKT promoted repair of the mucosal barrier. RT-qPCR for the amino acid transporters EAAT3 and BO+AT also confirmed that DKT promoted mucosal repair and thus promoted nutrient absorption.
CONCLUSION
DKT protected against MTX-induced CIM in a rat model by reducing inflammation, stimulating cell proliferation, and stabilizing the mucosal barrier.
背景
大建中汤（DKT）对改善各种胃肠道疾病有积极的治疗作用。本研究旨在探讨 DKT 是否对大鼠模型中化疗诱导的急性小肠粘膜炎（CIM）有潜在的治疗作用。
方法
采用腹腔注射 10mg/kg 甲氨蝶呤（MTX），每 3 天 1 次，共 3 次，诱导大鼠 CIM 模型。MTX 和 DKT-MTX 组于第 1 天开始按上述方法注射 MTX，DKT-MTX 和 DKT 组同时通过饮食给予 2.7% DKT。第 15 天处死大鼠。
结果
DKT-MTX 组的体重和胃肠道疾病状况得到改善，血浆和小肠绒毛中的二胺氧化酶水平升高。病理结果显示，DKT-MTX 组的小肠粘膜损伤程度较 MTX 组轻。髓过氧化物酶和丙二醛的免疫组化以及转化生长因子-β1（TGF-β1）和缺氧诱导因子-1α（HIF-1α）的定量实时聚合酶链反应（RT-qPCR）显示，DKT 减轻了过氧化损伤。DKT-MTX 组的隐窝中含有更多的 Ki-67 阳性细胞，比 MTX 组多。闭锁蛋白-1（zonula occluden-1）和闭合蛋白-3（claudin-3）的结果表明，DKT 促进了粘膜屏障的修复。氨基酸转运体 EAAT3 和 BO+AT 的 RT-qPCR 也证实了 DKT 促进了粘膜修复，从而促进了营养物质的吸收。
结论
DKT 通过减少炎症、刺激细胞增殖和稳定粘膜屏障，对大鼠模型中的 MTX 诱导的 CIM 起到保护作用。
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