藜芦酸通过激活 Nrf2/HO-1 信号通路减轻氧化应激缓解葡聚糖硫酸钠诱导的小鼠实验性结肠炎

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Abstract：ObjectiveToinvestigate themolecular mechanismbywhichveratricacid（VA）amelioratesoxidativestressinjury andintestinal barrer dysfunction in mice with dextransulfate sodium （DS）-induced colitis.Methods Thirty male C57BL/6 micewererandomizedequallintoontrolgroup，DSSmodel group，andVAtreatmentgroup.Themicewereassessedfor changes nbodyweight，diseaseactivityidex（DAl）colonlength，andcolonichistopathologyoloncexpresiosf- α∗ IL-6，and IL-10andoxidative stressmarkers （SOD，GSH，MDA，and COX-2）were determinedusing ELISA，andthe expresions of tight junctionproteins （ZO-1 and claudin-1）and Nrf2/HO-1 pathwayproteins were detected using immunofluorescence staining and Western blotting. In Caco-2 cells with H2O2 -induced oxidativestress，ROSaccumulationwas examinedusinflowcytometryandaDCFH-DAprobe，andNrf2inhibitor（ML385）wasusedtovalidatethemechanismof VA foramelioratingoxidativestress.ResultsVAtreatmentsignificantlyallviated DSS-induced body weight loss，colon shorteningandtheincreaseofDIscoreofthemice，resultingalsoinimprovedcryptstructureandincreasedexprionsof ZO-1and claudin-1and the number of gobletcels. VA obviously reduced colonic levelsof TNF- α and IL-6，increased the level of IL-10，andreversed DS-induceddecreases in SODand GSHactivityand increases in MDA andCOX-2 levels. In H2O2 -treated Caco-2cels，VAdecreasedROS-positivecellrateandintracellularROSacumulation，andincreasedcelular expresionsof claudin-1andZO-1Mechanistically VApromotedtheexpresionsofNrf2andthedowstramHO-1protein， andML385 partiallreversedROS-reducing effectofVA.Conclusion VAenhancesantioxidantdefense，inibitsinflammation， andrepairs intestinalbarrierfunctionin mice with DSS-inducedcolitisbyactivatingtheNrf2/HO-1pathwaysuggestinga novel strategy for treatment of inflammatory bowel disease.

words： inflammatoryboweldisease;veratricacid;Nrf2/HO-1signalingpathwayoidativestres;intestial

炎症性肠病（IBD）是以肠道慢性炎症和黏膜屏障进行性损伤为特征的复发性疾病，其亚型溃疡性结肠炎（UC）和克罗恩病（CD）的病理机制与氧化应激失衡密切相关[1-3]。（剩余15772字）