芳香烃受体（AhR）是由多种环境因子活化的细胞质转录因子。AhR激活参与肠黏膜动态平衡控制，并被认为可抑制炎性肠病（IBD）。其中，白细胞介素（IL）-10被证明是改善黏膜炎症的重要抗炎细胞因子。
为此，医院（第三医院）探讨了AhR及其激动剂吲哚并[3,2-B]咔唑-6-甲醛（FICZ）对葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎的缓解作用及其机制。
该研究将成年雄性C57BL/6小鼠随机分为正常对照组、DSS组（每天给予DSS喂养，连续7d）、DSS＋FICZ组（给予DSS喂养连续7d，从第3天开始腹腔注射FICZ）。每天检测小鼠体重变化，7d后HE染色观察结肠病理学变化，qPCR检测小鼠结肠上皮细胞炎性因子的表达。
结果发现，与正常对照组相比，模型组中小鼠体重明显减轻（P＜0.05），结肠长度缩短，肠黏膜明显损伤，促炎因子IL-1β、IL-6和肿瘤坏死因子（TNF）-α的表达升高（P＜0.05），保护性的细胞因子IL-10的表达变化不明显；与模型组相比，实验组中小鼠体重下降明显减少（P＜0.05），结肠长度增加，肠黏膜损伤减轻，同时促炎因子IL-1β、IL-6、TNF-α的表达降低（P＜0.05），保护性细胞因子IL-10明显升高（P＜0.05）。
因此，AhR对小鼠结肠炎具有抑制作用，可能是通过下调促炎因子IL-1β、IL-6和TNF-α的表达，上调抗炎因子IL-10的表达发挥作用。
JPENJParenterEnteralNutr.;41(2):.
ArylhydrocarbonreceptoractivationameliorateDSS-inducedcolitisthroughup-regulatetheexpressionofIEC-derivedIL-10.
LiangziLi,MinYu,WeidongXiao,HuaYang.
GeneralSurgery,XinqiaoHospital,Chongqing,China.
PURPOSE:Thearylhydrocarbonreceptor(AhR)isacytoplasmictranscriptionfactoractivatedbyalargevarietyofenvironmentalagents.ActivationoftheAhRisinvolvedinthecontrolofintestinalmucosalhomeostasisandthoughttosuppressinflammatoryboweldisease(IBD).Interleukin-10(IL-10)isprovedtobeanimportantanti-inflammatorycytokinethatamelioratesmucosalinflammation.ThegoalofthisstudywastoinvestigatetheroleofAhRactivationinalleviatingintestinalinflammationbyupregulatingIL-10inintestinalepithelialcells(IECs).
METHODS:AdultC57BL/6miceweretreatedwith3.5%dextransulfatesodium(DSS)for7days.ThemiceweregiveninjectionsoftheAhRligand6-formylindolo(3,2-b)carbazole(FICZ)starting2daysafterthefirstadministrationofDSS.Micewereweighted,colontissueswerecollectedandmeasured,andhistologyanalyseswereperformed.IECswereisolatedfromcolon,andtheexpressionofIL-10inIECswasassessedbyquantitativereal-timepolymerasechainreaction(qRT-PCR)andWesternblotanalysis.Caco-2intestinalepithelialcellsweretreatedwithlipopolysaccharide(LPS)for24hours,withorwithoutFICZ,andIL-10expressionwasdetectedbyWesternblotanalysisandqRT-PCR.Additionally,Caco-2cellsweretreatedwithAhRsiRNA,andexpressionofIL-10wasstudiedwithWesternblotanalysisandqRT-PCR.
RESULTS:AdministrationofFICZtomicewithDSS-inducedcolitisresultedasignificantincreaseinAhRexpressiondetectedbyWesternblotanalysisandqRT-PCR.HistologicalexaminationofcolonictissuesshowedthatmoreinjurywasobservedintheDSSgroupthanintheFICZ+DSSgroup.Furthermore,administrationofFICZgreatlydeceleratedtheweightlossinducedbyDSS.WesternblotanalysisandqRT-PCRshowedFICZsignificantlyincreasedtheexpressionofIEC-derivedIL-10bothinthecolonsofmicewithDSS-inducedcolitisandLPS-treatedCaco-2cells.FICZalsoincreasedtheexpressionofphosphorylatedSTAT3inLPS-treatedCaco-2cells.Interestingly,inhibitionofSTAT3phosphorylationbyStatticcounteractedFICZ-inducedincreaseofIL-10expressioninCaco-2cells.
CONCLUSIONS:FICZ-inducedAhRactivationcouldupregulatetheexpressionofIEC-derivedIL-10andameliorateDSS-inducedcolitis.AhR-related哪家白癜风能治愈北京哪间医院看白癜风最好
