Li Peilin, Inoue Yusuke, Sadatomi Daichi, Mogami Sachiko, Miyamoto Daisuke, Adachi Toshiyuki, Adachi Tomohiko, Soyama Akihiko, Kanetaka Kengo, Gu Weili, Eguchi Susumu
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.
Front Pharmacol. 2025 Aug 21;16:1623726. doi: 10.3389/fphar.2025.1623726. eCollection 2025.
Chronic small-intestinal mucositis (CIM) is a severe gastrointestinal complication that has limited treatment options. This study investigated the potential therapeutic effects of Daikenchuto (DKT), a traditional medicine, on mitigating methotrexate (MTX)-induced CIM in rats.
Male Sprague-Dawley rats were assigned to four groups: control, MTX, DKT-MTX, and DKT. CIM was induced by intraperitoneal administration of MTX (10 mg/kg every 6 days), while DKT (2.7% wt/wt) was orally administered via feed. The surviving rats were euthanized on day 60. Rat intestinal epithelial cells (IEC-6) were used to examine DKT's cytoprotective effects .
DKT treatment improved survival, reduced gastrointestinal symptoms, and alleviated histological damage, including villus atrophy and crypt hyperplasia. DKT restored mucosal integrity by enhancing the expression of tight junction proteins (CLDN-3) and nutrient transporters (B0,+AT, EAAT3), and by reducing oxidative stress and epithelial cell death. Furthermore, DKT promoted mucosal angiogenesis, as evidenced by increased expression of CD34, VEGFR2, and VEGFA in both tissues and cells. qRT-PCR confirmed upregulation of genes associated with angiogenesis, barrier repair, and mucosal regeneration.
DKT exerts protective effects against MTX-induced CIM by enhancing angiogenesis, promoting epithelial regeneration, and restoring mucosal barrier function. These findings suggest DKT as a promising adjunctive therapy for managing chronic intestinal toxicity induced by chemotherapy.
慢性小肠黏膜炎（CIM）是一种严重的胃肠道并发症，治疗选择有限。本研究调查了传统药物大建中汤（DKT）对减轻甲氨蝶呤（MTX）诱导的大鼠CIM的潜在治疗效果。
将雄性Sprague-Dawley大鼠分为四组：对照组、MTX组、DKT-MTX组和DKT组。通过腹腔注射MTX（每6天10mg/kg）诱导CIM，而DKT（2.7%重量/重量）通过饲料口服给药。存活的大鼠在第60天安乐死。使用大鼠肠上皮细胞（IEC-6）检查DKT的细胞保护作用。
DKT治疗提高了存活率，减轻了胃肠道症状，并减轻了组织学损伤，包括绒毛萎缩和隐窝增生。DKT通过增强紧密连接蛋白（CLDN-3）和营养转运蛋白（B0，+AT，EAAT3）的表达，以及通过减少氧化应激和上皮细胞死亡，恢复了黏膜完整性。此外，DKT促进了黏膜血管生成，组织和细胞中CD34、VEGFR2和VEGFA表达增加证明了这一点。qRT-PCR证实了与血管生成、屏障修复和黏膜再生相关基因的上调。
DKT通过增强血管生成、促进上皮再生和恢复黏膜屏障功能，对MTX诱导的CIM发挥保护作用。这些发现表明DKT是治疗化疗引起的慢性肠道毒性的一种有前景的辅助疗法。
