首页|期刊导航|海南医科大学学报|4-二乙氨基苯甲醛诱导肠道屏障稳态失调的机制研究

4-二乙氨基苯甲醛诱导肠道屏障稳态失调的机制研究OA

Mechanism of 4-diethylaminobenzaldehyde-induced disruption in gut barrier homeostasis

中文摘要英文摘要

目的:探讨 4-二乙氨基苯甲醛(4-diethylaminobenzaldehyde,DEAB)对小鼠肠道上皮屏障的影响,研究相关分子机制.方法:12只成年雄性 C57BL/6小鼠随机分为对照组及 DEAB组.DEAB组给予10 mg∙kg-1∙bw-1 DEAB腹腔注射,对照组给予玉米油腹腔注射.7 d后,采用H&E染色和PAS染色观察小鼠肠道组织病理形态表现;组织免疫荧光染色检测肠道上皮组织Lgr5、ZO-1蛋白表达量;RT-PCR检测肠道上皮细胞IL-22、Reg3γ、Reg3β、Lgr5 mRNA表达量;流式细胞术检测肠道固有层淋巴细胞中CD11c+MHC-Ⅱ+细胞、CD3+细胞数量;平板法检测肠系膜淋巴结及脾脏载菌量.结果:相较于对照组,DEAB组小鼠肠绒毛长度明显缩短,肠道炎症细胞明显增多,杯状细胞明显减少(P<0.05);肠道上皮隐窝Lgr5蛋白及ZO-1蛋白表达明显减少(P<0.01);小鼠肠道上皮细胞IL-22、Reg3γ、Reg3β mRNA表达水平明显升高(P<0.05),而Lgr5 mRNA表达水平明显降低(P<0.05);小鼠肠道固有层淋巴细胞中CD11c+MHC-Ⅱ+细胞和CD3+细胞数量明显增多(P<0.05);小鼠肠系膜淋巴结以及脾脏载菌量明显升高(P<0.01).结论:视黄酸代谢通路失调导致肠道免疫细胞数量异常,肠道屏障功能受损,细菌感染风险增加,其机制可能与Lgr5蛋白表达失调及紧密连接破坏有关.

Objective:To investigate the effects of 4-diethylaminobenzaldehyde(DEAB)on the intestinal epithelial barrier in mice and to explore the underlying molecular mechanisms.Methods:A total of 12 adult male C57BL/6 mice were randomly divid-ed into a control group and a DEAB group.The DEAB group received intraperitoneal injections of 10mg∙kg-1∙bw-1 DEAB,and the control group received intraperitoneal injections of corn oil.After 7 days,H&E staining and PAS staining were performed to ob-serve histopathological changes in mice intestinal tissues.Immunofluorescence staining was used to measure the expression levels of Lgr5 and ZO-1 proteins in the intestinal epithelium.RT-PCR was employed to detect mRNA expression levels of IL-22,Reg3γ,Reg3β,and Lgr5 in intestinal epithelial cells.Flow cytometry was used to quantify CD11c+MHC-Ⅱ+cells and CD3+cells in the intestinal lamina propria lymphocytes.The bacterial load in mesenteric lymph nodes and spleen was assessed using plate counting.Results:Compared to the control group,DEAB-treated mice exhibited significantly shorter intestinal villi,increased in-flammatory cells,and reduced goblet cells(P<0.05).The expression of Lgr5 and ZO-1 proteins in intestinal crypts was signifi-cantly decreased(P<0.01).The mRNA expression levels of IL-22,Reg3γ,and Reg3β in intestinal epithelial cells were signifi-cantly elevated(P<0.05),and the mRNA expression level of Lgr5 was decreased(P<0.05).The numbers of CD11c+MHC-Ⅱ+cells and CD3+cells in the intestinal lamina propria lymphocytes were significantly increased(P<0.05).The bacterial load in mes-enteric lymph nodes and spleen was significantly elevated(P<0.01).Conclusion:Dysregulation of the retinoic acid metabolic pathway leads to abnormal numbers of intestinal immune cells,impaired intestinal barrier function,and increased risk of bacterial infection.The underlying mechanism may be associated with dysregulated Lgr5 protein expression and disruption of tight junctions.

蓝楠;唐红梅;李柏均;李月蛟;王孝芸;袁谢芳

西南医科大学附属医院呼吸与危重症医学科,四川 泸州 646000||西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000西南医科大学附属医院炎症与变态反应实验室,四川 泸州 646000

医药卫生

视黄酸4-二乙氨基苯甲醛(DEAB)Lgr5肠道感染

Retinoic acid4-diethylaminobenzaldehyde(DEAB)Lgr5Intestinal infection

《海南医科大学学报》 2026 (11)

801-806,6

This study was supported by the National Natural Science Foundation of China(82001703)Natural Science Foundation Project of Sichuan Province(2023NSFSC1620) 国家自然科学基金(82001703)四川省自然科学基金(2023NSFSC1620)

10.13210/j.cnki.jhmu.20260226.001

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