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目的研究全反式视黄酸(all-trans retinoic aciol,ATRA)与1,25-(OH)_2D_3联合作用对葡聚糖硫酸钠(DSS)诱导的溃疡性结肠炎小鼠辅助性T细胞17(Thelper17cells,Th17)细胞相关因子表达的影响。方法 50只6周龄雌性SPF级C57BL/6小鼠随机分为对照组、模型组、ATRA组、1,25-(OH)_2D_3组与ATRA+1,25-(OH)_2D_3联合组。对照组饮用蒸馏水,其余组饮用3.0%DSS溶液造模。造模第3天起对3个干预组分别灌胃给予0.2mg/d/只ATRA或/和100ng/d/只1,25-(OH)_2D_3。第9天处死小鼠,取结肠组织,进行大体形态学评分;HE染色进行组织病理学评分;免疫组织化学法检测结肠IL-17、IL-23表达;ELISA测定结肠维甲酸相关核孤儿受体γt(retinoid acid receptor related orphan receptors,RORγt)、IL-6和TGF-β表达。采用单因素方差分析进行组间比较,采用析因设计方差分析判断两因素联合是否有交互作用。结果3个干预组与模型组比较,疾病活动指数(disease activity index,DAI)、大体形态和组织病理学评分均降低,IL-17、RORγt,IL-23及IL-6表达量下降,ATRA+1,25-(OH)_2D_3联合干预组效果更显著(P<0.05)。结论联合应用ATRA和1,25-(OH)_2D_3能更有效地抑制Th17相关因子的表达,减轻炎症,缓解结肠炎症状。
Objective To investigate the effect of all-trans retinoic aciol (ATRA) and 1,25- (OH) _2D_3 on dextran sulfate sodium (DSS) -induced murine helper T cells in mice with ulcerative colitis (Thelper17cells, Th17) cell-related factor expression. Methods Fifty 6-week old female SPF C57BL / 6 mice were randomly divided into control group, model group, ATRA group, 1,25- (OH) _2D_3 group and ATRA + 1,25- (OH) _2D_3 group. Control group drinking distilled water, the remaining group drinking 3.0% DSS solution modeling. On the third day after modeling, 0.2mg / d / ATRA or / and 100ng / d / only 1,25- (OH) _2D_3 were given intragastrically to the three intervention groups respectively. The mice were sacrificed on the 9th day, and the colon tissues were harvested for gross morphology score. Histopathological score was determined by HE staining. The expressions of IL-17 and IL-23 in colon were detected by immunohistochemistry. The levels of IL- γt (retinoid acid receptor related orphan receptors, RORγt), IL-6 and TGF-β expression. One-way analysis of variance (ANOVA) was used to compare between groups. Factorial analysis of variance (ANOVA) was used to determine whether there was interaction between the two factors. Results Compared with the model group, the disease activity index (DAI), gross morphology and histopathological score decreased, the expression of IL-17, RORγt, IL-23 and IL-6 decreased and the levels of ATRA + 1,25- (OH) _2D_3 joint intervention group was more significant (P <0.05). Conclusion Combined application of ATRA and 1,25- (OH) _2D_3 can inhibit the expression of Th17-related factor, reduce the inflammation and relieve the symptoms of colitis more effectively.