芳香烃受体缺失对实验性结肠炎的影响及其机制
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国家自然科学基金(81470827,81770553)


Effects of loss of aryl hydrocarbon receptor on experimental colitis and its mechanism
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    摘要:

    目的:探讨芳香烃受体(aryl hydrocarbon receptor,AhR)缺失在小鼠肠道炎症发生发展中的作用及可能机制。 方法:将实验对象分为4组:野生型对照组(WT control)、野生型肠炎组(WT TNBS)、AhR敲基因对照组(AhR-/- control)和AhR敲基因肠炎组(AhR-/- TNBS)(每组6只)。用2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzenesulfonic acid,TNBS)建立小鼠急性结肠炎模型,比较各组小鼠疾病活动指数(disease activity index,DAI)、结肠长度和组织病理学表现。免疫印迹和免疫荧光实验检测小鼠肠组织中调节性T细胞(regulatory T cell,Treg)特异性转录因子FoxP3的表达水平,流式细胞术检测小鼠外周血Treg细胞比例。结果:相比于WT小鼠,AhR-/-小鼠TNBS造模后肠炎更为严重,体重明显减轻(P < 0.01),腹泻、便血症状更为突出,DAI评分更高(P < 0.001),结肠明显缩短(P < 0.01),组织学评分更重(P < 0.001)。同时,AhR-/- TNBS小鼠肠组织FoxP3表达下降(P < 0.01),外周血Treg细胞比例降低(P < 0.01)。结论:AhR缺失能加重小鼠实验性结肠炎肠道炎症,该作用可能与小鼠肠组织和外周血中Treg细胞减少有关。

    Abstract:

    Objective:To investigate the effect of loss of aryl hydrocarbon receptor(AhR) on intestinal inflammation and its potential mechanism. Methods:Mice were assigned into 4 groups:wild type control group(WT control),wild type colitis group(WT TNBS),AhR knockout control group(AhR-/- control) and AhR knockout colitis group(AhR-/- TNBS). Acute experimental colitis was established using 2,4,6-trinitrobenzenesulfonic acid(TNBS). Disease activity index(DAI)score,colon length and histological score were compared among different groups. The expression of regulatory T cell(Treg) specific transcription factor FoxP3 was measured by Western blot(WB) and immunofluorescence(IF). Proportion of Treg cells in peripheral blood was detected by flow cytometry. Results:Compared with WT mice,AhR-/- mice experienced much more severe colitis after TNBS administration,manifested by more weight loss(P < 0.01),severe diarrhea and bloody stool,higher DAI score(P < 0.001),shorter colon length(P < 0.01) and poorer histological findings(P < 0.001). Also,expression of FoxP3 in the colon and proportion of Treg cells in peripheral blood were much lower in AhR-/- TNBS mice(P < 0.01). Conclusion:Deletion of AhR was found to aggravate experimental colitis. This effect could be associated with the decrease of Treg cells in the colon and peripheral blood.

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李佳佳,赵小静,马晶晶,崔秀芳,王 迪,张红杰.芳香烃受体缺失对实验性结肠炎的影响及其机制[J].南京医科大学学报(自然科学版),2020,(7):956-962

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  • 收稿日期:2019-12-03
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  • 在线发布日期: 2020-08-05
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