珠子草素通过调控p38/JNK信号通路抑制肠上皮细胞凋亡保护肠屏障改善克罗恩病样肠炎

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Abstract： ObjectiveToinvestigatethetherapeuticefectof thenaturalcompoundniranthinonCrohn'sdisease-likecolitisin mice and explore the underlying molecular mechanisms.Methods In a mouse model of colitis induced by 2，4，6 -trinitrobenzenesulfonicacid （TNBS），the therapeutic efect of niranthin was evaluated byobserving the changes inbody weight， diseaseactivityindex （DAI），andcolonlengthofthemice.Thelevelsofinflammatorycytokines （IL-6，IL-1β，F- αι IL-17A and IL-10）inthe intestinal mucosal tissue were detected using ELISA and quantitativereal-time PCR （qRT-PCR）.TUNEL stainingandWesternblotingwereusedtoassessintestinalepithelialcellapotosisandtheexpresonsofcl-2andBax.The expresion levelsof tight junction proteins （ZO-1and claudin-1）andtheactivationof the p38/JNK signaling pathway were investigatedusing Westernblotinganddiprovociminterventionexperimentswereconducted toexplorethemolecular regulatorymechanismof niranthin.ResultsNiranthintreatmentsignificantlyincreasedbody weightofTNBS-treatedmice， loweredtheDAIandhistologicalinflammationscores，andincreasedcolonlengthofthemice.Theniranthin-treatedmouse modelsshowed obviouslyreduced proteinandmRNAlevels ofIL-6，IL-1β，IL-17A，and NF- α and upregulated expression of IL-10in thecolontissue.TUNELstainingandWesternblotting demonstratedthatniranthinsignificantlyinhibited intestinal epithelialcellapoptosisandactivated theanti-apoptoticpathwayinthemousemodels.Niranthintreatmentobviously upregulated theexpresionlevelsofZO-1andclaudin-1anddownregulatedthephosphorylationlevelsof p38andJNKinthe colontissues of the mice. Diprovocim intervention obviouslyatenuated the inactivation of thep38/JNK signaling pathway inducedbyniranthininthemousemodels.ConclusionNiranthinamelioratesTNBS-inducedCrohn'sdisease-likecolitisin micebyinhibitingintestinalepithelialcellapoptosisandprotectingtheintegrityoftheintestialbarierviaregulatingthe activation of the p38/JNK signaling pathway.

Keywords：Crohn'sdisease;inlammatoryoweldisease;intestinalepithelialcellapoptosis;p38/NK;Nirathin

克罗恩病（CD）是一种以慢性透壁性炎症为特征的炎症性肠病（IBD），病变多累及回肠末端及结肠，临床表现为反复腹痛、腹泻、体质量减轻及肠外并发症，严重影响患者生存质量[-3]。（剩余16809字）