刺桐碱通过抑制肠上皮炎症反应并改善肠屏障功能缓解小鼠克罗恩病样结肠炎

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Abstract：ObjectiveToinvestigatetheefectof hypaphorine （HYP）onCrohn'sdisease（CD）-likecolitisinmiceandits molecularmechanism.MethodsTirtymaleC57BL/6JmicewereequalyrandomizedintoWT，TNBS，andHYPgroupsandin th later two groups，mouse models ofCD-likecolitis were establishedusing TNBS with daily gavageof15 mg/kg HYPoran equivalent volumeofsaline.The treatmenteficacy was evaluatedbyassessng the disease activityindex （DAI），bodyweight changes，colonlengthandhistopathology.TheeffctofHYPwasalsotestedinaLPS-stimulatedCaco-2cellmodelmimicking intestinal inflammationbyevaluating inflammatoryresponsesandbarier functionof thecelsusing qRT-PCR and immunofluorescencestaining.GOand KEGGanalyseswereconducted toexplorethetherapeutic mechanismof HP，which Was validatedinboththecellandmouse modelsusingWesternbloting.Results InthemousemodelsofCD-likecolitis，HYP interventionobviouslyallviatedcolitisasshown bysignificantlyreduced bodyweightloss，colon shorteningDAIand inflammationscores，andexpressionsofproinflammatoryfactorsintheolontissues.HYPtreatmentalsosigniicantly increasedtheERluesducedacterialtraslocationtothemeseteriphodes，livendsleen，lowedu levelsofI-FABPndFCdextra，increasedtheumberofcolonic tuecupcelsandupregulatedcolonicexpriosof MUC2 and tight junction proteins （claudin-1andZO-1） inthe mouse models.InLPS-stimulatedCaco-2 cels，HYtreatment significantlyinibitedtheexpresionsofpro-inflammatoryfactorsandincreasedtheexpressionsoftightjunctionproteins. Western blotting showed thatHYP downregulated the expressions of thekey proteins in the TLR4/MyD88 signaling pathway in boththe invitroandinvioomodels.Conclusion HYaleviates CD-likecolitis inmice possblybysuppressing intestinal epithelial inflammation and improving gut barrier function.

Keywords： Crohn'sdisease;colitis;hypaphorine;intestinal barrier;intestinal epithelial cells

克罗恩病（CD）是炎症性肠病（IBD）的主要亚型之一，其典型病理特征为肠道免疫失衡和透壁性炎症。（剩余17755字）