中国药理学通报2025，Vol.41Issue(5)：830-836,7.DOI:10.12360/CPB202410058
别嘌呤醇恢复犬尿氨酸异常代谢改善小鼠溃疡性结肠炎的作用和机制
Role and mechanism of allopurinol in restoring abnormal metabolism of kynurenine to alleviate ulcerative colitis in mice
摘要
Abstract
Aim To investigate the role and mecha-nism of allopurinol(ALLO)in restoring the abnormal metabolism of kynurenine(Kyn)mediated by trypto-phan-2,3-dioxygenase 2(TDO2)to ameliorate ulcera-tive colitis(UC)in mice,and to provide experimental basis for the treatment of UC by ALLO.Methods A dextran sodium sulfate(DSS)-induced mouse UC mod-el was established,and the mice were randomly divided into the control group,the model group,the ALLO low,medium and high-dose groups(10,20,and 40 mg·kg-1),and the positive-significant salazosulfapyridine(SASP)(200 mg·kg-1)group.The body mass and disease activity index(DAI)scores of mice were re-corded;HE staining was performed to observe the de-gree of pathological damage in colon tissue;Western blot was performed to detect TDO2 protein expression in colon tissue;flow cytometry was performed to detect changes in the proportion of macrophages in spleen and mesenteric lymph nodes;ELISA was employed to de-tect the levels of TNF-α,IL-1β and IL-6 pro-inflamma-tory cytokines in the supernatant of colon tissue homog-enate;high performance liquid chromatography(HPLC)was used to detect the levels of tryptophan(Trp)and Kyn in the supernatant of colon tissue ho-mogenate.Results Compared with the model group,ALLO administration significantly ameliorated colonic histopathological injury in UC mice,decreased the pro-portion of macrophages in spleen and mesenteric lymph nodes,down-regulated the levels of TNF-α,IL-1 β,and IL-6 pro-inflammatory factors in serum of homogenate of colonic tissues,and inhibited the activity(Kyn/Trp ratio)and expression of TDO2 in colonic tissues.Con-clusion ALLO improves disease manifestations in mice with ulcerative colitis,which may be related to its restoration of abnormal Kyn metabolism.关键词
溃疡性结肠炎/别嘌呤醇/犬尿氨酸/色氨酸/色氨酸-2,3-双加氧酶2/自身免疫病Key words
ulcerative colitis/allopurinol/kynurenine/tryptophan/tryptophan-2,3-dioxygenase 2/autoim-mune disease分类
医药卫生引用本文复制引用
陈悦兰,董伟波,许和鹏,严尚学,魏伟,常艳..别嘌呤醇恢复犬尿氨酸异常代谢改善小鼠溃疡性结肠炎的作用和机制[J].中国药理学通报,2025,41(5):830-836,7.基金项目
国家自然科学基金资助项目(No 81973332) （No 81973332）
安徽省自然科学基金面上项目(No 2108085MH320) （No 2108085MH320）
安徽省留学人员创新项目择优资助计划项目(No 200LCX019) （No 200LCX019）
安徽省高校科研项目(No 2024AH050745) （No 2024AH050745）
安徽省转化医学研究院科研基金项目(No 2023zhyx-C11) （No 2023zhyx-C11）
