中国中医急症2026,Vol.35Issue(5):521-527,7.DOI:10.3969/j.issn.1004-745X.2026.05.005
YTHDC1介导的XBP1 m6A修饰在解毒化瘀汤促进自噬治疗溃疡性结肠炎中的机制研究
Study on the Mechanism of Jiedu Huayu Decoction Promoting Autophagy in the Treatment of Ulcerative Colitis Based on YTHDC1-Mediated XBP1 m6A Modification
摘要
Abstract
Objective:To explore the mechanism of Jiedu Huayu Decoction regulating autophagy in the treat-ment of ulcerative colitis(UC)based on YTHDC1-mediated XBP1 mRNA m6A methylation modification.Meth-ods:Sixty SD rats were randomly divided into the control group,model group,low-,medium-and high-dose Jie-du Huayu Decoction groups,and positive drug group.UC model was established by allowing free access to 5%dex-tran sulfate sodium(DSS)for 7 days,while intragastric administration was given simultaneously during the same period.Pathological changes of colon tissue were observed by HE staining;serum inflammatory factor levels were detected by enzyme-linked immunosorbent assay(ELISA);ultrastructure of colon tissue was observed by transmis-sion electron microscope;the expression of autophagy-related proteins,YTHDC1 and XBP1s was detected by West-ern blotting;the mRNA expression of YTHDC1 and XBP1 was detected by quantitative reverse transcription-poly-merase chain reaction(qRT-PCR);the m6A modification level of XBP1 mRNA was detected by MeRIP-qPCR.Results:Compared with the model group,all dose groups of Jiedu Huayu Decoction significantly improved DSS-in-duced colon tissue injury,and reduced inflammatory score and serum pro-inflammatory factor levels(P<0.01).Meanwhile,Jiedu Huayu Decoction dose-dependently increased the number of autophagosomes in colonic epitheli-al cells,up-regulated the ratios of LC3-Ⅱ/Ⅰ and p-AMPK/AMPK,and down-regulated the expression of p62 and the ratio of p-mTOR/mTOR(P<0.01).In addition,Jiedu Huayu Decoction significantly up-regulated the pro-tein and mRNA expression of YTHDC1,the protein expression of XBP1s and mRNA expression of XBP1 in colon tissue of model rats(P<0.01),and reversed the down-regulation of XBP1 mRNA m6A modification level induced by DSS,with statistically significant differences(P<0.01).Conclusion:Jiedu Huayu Decoction may up-regulate YTHDC1 expression,increase m6A modification of XBP1 mRNA,thereby elevate the level of XBP1s protein,acti-vate AMPK/mTOR pathway-mediated autophagy,inhibit intestinal inflammation,and exert therapeutic effect on UC.关键词
溃疡性结肠炎/解毒化瘀汤/YTHDC1/m6A甲基化/自噬/大鼠Key words
Ulcerative colitis/Jiedu Huayu Decoction/YTHDC1/m6A methylation/Autophagy/Rats分类
医药卫生引用本文复制引用
刘颖,王鹏,袁星星,李丽萍..YTHDC1介导的XBP1 m6A修饰在解毒化瘀汤促进自噬治疗溃疡性结肠炎中的机制研究[J].中国中医急症,2026,35(5):521-527,7.基金项目
中华中医药学会青年培英计划项目(202557-011) (202557-011)
北京医卫健康公益基金会医学科学研究基金项目(YWJKJJHKYJJ-B2025032601) (YWJKJJHKYJJ-B2025032601)