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miRNA调控claudin-2表达对溃疡性结肠炎小鼠巨噬细胞极化的机制

MiRNA regulates macrophage polarization in mice with ulcerative colitis by mediating claudin-2
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摘要 目的探讨微小核糖核酸(MicroRNA,miRNA)通过封闭蛋白2(Recombinant,claudin-2)表达变化对溃疡性结肠炎小鼠的保护作用及对巨噬细胞极化的调控。方法选取BALB/c雌性小鼠按照体重随机分成对照组、模型组以及上调组和下调组,每组15只。对4组小鼠溃疡性结肠组织进行HE染色,观察分析小鼠溃疡性结肠炎评分情况、炎性因子、免疫细胞、巨噬细胞、claudin-2表达。结果与对照组比较,模型组、上调组、下调组miRNA表达升高(P<0.05);与模型组比较,上调组miRNA表达降低、下调组升高(P<0.05);与上调组比较,下调组miRNA表达升高(P<0.05);与模型组比较,上调miRNA第3 d、5 d、7 d的溃疡性结肠炎模型小鼠明显降低、下调组升高;与上调组比较,下调组miRNA表达升高(P<0.05);与对照组比较,模型组、上调组、下调组T淋巴细胞的糖蛋白(CD4^(+))、白细胞分化抗原(CD8^(+))水平升高(P<0.05);与模型组比较,上调组CD4^(+)、CD8^(+)水平降低,下调组升高(P<0.05);与上调组比较,下调组CD4^(+)、CD8^(+)水平升高(P<0.05);与对照组比较,模型组、上调组、下调组肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、白介素-8(IL-8)水平升高(P<0.05);与模型组比较,上调组TNF-α、IL-6、IL-8水平降低(P<0.05);与上调组比较,下调组升高(P<0.05);与对照组比较,模型组、上调组、下调组诱导型一氧化氮合酶(iNOS)水平升高,巨噬细胞甘露糖受体(CD206)降低(P<0.05);与模型组比较,上调组iNOS水平降低、CD206水平升高,下调组iNOS水平升高、CD206水平降低(P<0.05);与上调组比较,下调组iNOS升高、CD206降低(P<0.05);与对照组比较,模型组、上调组、下调组claudin-2蛋白表达升高(P<0.05);与模型组比较,上调组claudin-2蛋白表达降低、下调组claudin-2蛋白表达升高(P<0.05)。结论上调溃疡性结肠炎小鼠miRNA能够调节巨噬细胞极化,从而改善溃疡性结肠炎小鼠。 Objective To explore the protective effect of microRNA(miRNA)on mice with ulcerative colitis(UC)and its regulatory effect on macrophage polarization by mediating claudin-2.Methods Female BALB/c mice were randomly divided into control,model,upregulation group and downregulation group based on the body weight,with 15 mice in each group.Colon tissues were subjected to hematoxylin and eosin(H&E)staining.Scores of UC,inflammatory factors,immune cells,macrophages,and claudin-2 expression were analyzed.Results Compared with that of the control group,the expression of miRNA in the model group,upregulation group and downregulation group was significantly higher (P<0.05).Compared with that of the model group,the expression of miRNA in the upregulation group significantly decreased and that in the downregulation group significantly increased(P<0.05).Compared with that of the upregulation group,the expression of miRNA in the downregulation group was significantly higher (P<0.05).Compared with that of the model group,the expression of miRNA on day 3,5 and 7 in UC mice of upregulation group was significantly lower,which was significantly higher in downregulation group(P<0.05).Compared with that of the upregulation group,the expression of miRNA in the downregulation group was significantly higher (P<0.05).Compared with those of the control group,the glycoprotein(CD4^(+))and leukocyte differentiation antigen(CD8^(+))of T lymphocytes in the model group,upregulation group,and downregulation significantly increased(P<0.05).Compared with those of the model group,CD4^(+)and CD8^(+)levels in the upregulation group significantly decreased,but significantly increased in the downregulation group(P<0.05).Compared with those of the upregulation group,CD4^(+)and CD8^(+)levels were significantly higher in the downregulation group(P<0.05).Compared with those of the control group,tumor necrosis factor (TNF-α),interleukin-6(IL-6)and interleukin-8(IL-8)levels in the model group,upregulation group,and downregulation group significantly increased(P<0.05).Compared with those of the model group,TNF-α,IL-6 and IL-8 levels in the upregulation group were significantly lower (P<0.05).Compared with those of the upregulation group,TNF-α,IL-6 and IL-8 levels in the downregulation group were significantly higher (P<0.05).Compared with those of the control group,the level of inducible nitric oxide synthase(iNOS)significantly increased and the macrophage mannose receptor (CD206)significantly decreased in the model group,upregulation group and downregulation group(P<0.05).Compared with those of the model group,the iNOS level in the upregulation group decreased and the CD206 level increased,while the iNOS level in the downregulation group increased and the CD206 level decreased significantly(P<0.05).Compared with those of the upregulation group,the iNOS level in the downregulation group increased and CD206 level decreased significantly(P<0.05).Compared with that of the control group,protein expression of claudin-2 in the model group,upregulation group and downregulation group significantly increased(P<0.05).Compared with that of the model group,protein expression of claudin-2 in the upregulation group decreased,but increased significantly in the down-regulation group(P<0.05).Conclusion Upregulation of ulcerative colitis mice with miRNA is able to regulate macrophage polarization and thereby ameliorates ulcerative colitis.
作者 朱卫 曾婷婷 ZHU Wei;ZENG Tingting(Department of Anorectal,the First Hospital of Hunan University of Chinese Medicine,Hunan,Changsha 410007,China)
出处 《河北医药》 CAS 2024年第2期176-180,共5页 Hebei Medical Journal
基金 湖南省卫生健康委员会科研计划(编号:B202304138985)。
关键词 微小RNA claudin-2 血清炎性因子 免疫细胞 溃疡性结肠炎 巨噬细胞极化 microRNA(miRNA) claudin-2 serum inflammatory cytokines immune cells ulcerative colitis macrophage polarization

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