研究动态
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搁置秦联煎剂 (GQD) 通过在小鼠和器官体中调节铁死亡依赖性通路来抑制溃疡性结肠炎。

Gegen Qinlian decoction (GQD) inhibits ulcerative colitis by modulating ferroptosis-dependent pathway in mice and organoids.

发表日期:2023 Aug 30
作者: Xue Wang, Jianye Quan, Chengkui Xiu, Jiali Wang, Jiaqi Zhang
来源: Chinese Medicine

摘要:

清炼合剂(GQD)是传统中医治疗溃疡性结肠炎(UC)的经典处方。然而,其治疗机制尚未完全阐明。本研究旨在通过使用DSS诱导的结肠炎小鼠模型和RSL3诱导的肠道器官小体的铁过氧化物介导的IEC细胞死亡,评估GQD对UC治疗小鼠中的作用。通过观察每日体重、DAI、结肠长度、HE染色、PAS染色、ZO-1和Occludin免疫组织化学染色,检测了GQD对DSS处理的结肠炎的影响。通过分析铁负荷、MDA、GSH、线粒体形态和铁过氧化物相关蛋白(GPX4、SLC7A11和ACSL4)的表达,确定了铁过氧化物的存在。在体内,GQD给药减轻了体重损失和DAI分数,增加了结肠长度,并改善了肠道的组织学特征和上皮屏障功能障碍。GQD给药明显改善了铁过氧化物标志物(铁负荷、MDA、GSH和线粒体形态)的水平以及铁过氧化物相关蛋白(GPX4、SLC7A11和ACSL4)的表达。与体内结果一致,GQD给药部分逆转了RSL3诱导的肠道器官小体中的mtROS、Fe2+和MDA水平,并明显改善了器官小体的形态破坏、组织损伤和上皮屏障功能障碍。本研究证明了DSS诱导的实验性结肠炎中触发了铁过氧化物,并且GQD给药通过抑制铁过氧化物来保护结肠损伤和肠道上皮屏障功能障碍。 © 2023. 国际中医学会和BioMed Central有限公司。
Gegen Qinlian decoction (GQD) is a classic prescription for treating ulcerative colitis (UC) in traditional Chinese medicine. However, the therapeutic mechanism has not been fully clarified.In the present study, we aimed to evaluate the role of ferroptosis-mediated IEC death in UC treated mice with GQD by using DSS-induced a colitis mouse model and RSL3-induced ferroptosis in intestinal organoids.The effects of GQD on DSS-treated colitis were examined via daily body weight, DAI, colon length, HE staining, PAS staining, ZO-1 and Occludin immunohistochemical staining. Ferroptosis was determined by analysis of iron load, MDA, GSH, mitochondrial morphology, and expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4).In vivo, GQD administration reduced body weight loss and DAI scores, increased colon length, and improved intestinal histological characteristics and epithelial barrier dysfunction. GQD administration obviously improved the levels of ferroptosis markers (iron load, MDA, GSH, and mitochondrial morphology) and the expression of ferroptosis-associated proteins (GPX4, SLC7A11 and ACSL4). Consistent with in vivo results, GQD administration partially reversed the levels of mtROS, Fe2+ and MDA in intestinal organoids induced by RSL3, and notably improved morphological destruction, histological damage and epithelial barrier dysfunction in organoids.In this study, we demonstrated that ferroptosis was triggered in DSS-induced experimental colitis and that GQD adiministration could protect against colonic damage and intestinal epithelial barrier dysfunction by inhibiting ferroptosis.© 2023. International Society for Chinese Medicine and BioMed Central Ltd.