马鞭草苷通过抑制PI3K-AKT通路减轻肠上皮炎症改善小鼠克罗恩病样结肠炎

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Abstract：ObjectiveToinvestigatethetherapeuticefectofverbenalin（VE）onCrohn'sdisease（CD）-likecolitisandthe underlying molecular mechanism.Methods FiftyC57BL/6 mice wererandomlydivided into control group，TNBS group，and low-，medium-，and high-dose VE treatment groups（ n=10） .Mouse modelsof CD-likecolitiswereestablished inall but the control group by enema with 25mg/L TNBS dissolved in ethanol， and the mice in VE treatment groupsreceived daily intraperitoneal injectionsofVEat 5，10，or 20mg/kg for7days. Cultured colon organoids derived from mouse cryptswere exposed to 100μg/mL lipopolysaccharide （LPS） for 24h andtreatedwith5，0，or 20μmol/L VE.The therapeutic effects of VE inthemousemodelsereevaluatedbyssessngangesinseaseactivitydex，stopathologicalsoress index.Inbotholonicmucosaoftemousemodelsandthecolonorganoids，thelevelsofinflammatorycytokines，xpsio of tightjunctionproteins，andchangesinPI3K-AKTpathwayproteins wereanalyzed，andtheregulatorymechanismof VE wasverifiedusingthePI3K-AKTagonist740Y-P.ResultsInTNBS-treatedmice，VEtreatmentsignificantlyreducedDAI histopathological scores，andspleen index，and mitigatedweightloss，colonshorteningandbacterial translocation.VE obviously lowered the expression of pro-inflammatorycytokines in colonicmucosa of the miceandthe colon organoids， upregulated ZO-1andclaudin-1expreions，andreducedbacterialtranslocation.VEsignificantlydownregulatedp-3Kand p-AKT proteinexpresions，whichwasreversedbytreatment with740Y-P.Conclusion VEinhibitsintestinalinflammation and protects intestinal barier function in mice with CD-like colitis by modulating the PI3K-AKT signaling pathway. Keywords：Crohn'sdisease;inflammatoryboweldisease;intestinalbarrier;PI3K-AKT;verbenalin

克罗恩病（CD）是一种慢性炎症性肠道疾病，发病率逐年上升，其临床表现多为腹痛、腹泻及肠梗阻等，严重影响患者生活质量[1-3]。（剩余14796字）