CDC42在慢性结肠炎小鼠发病中的作用及可能机制(1)
[摘要] 目的 探讨CDC42在慢性结肠炎小鼠结肠中的变化及与淋巴细胞因子水平的关系。 方法 36 只C57BL/6小鼠随机分为对照组、模型组和美沙拉嗪干预组 ，每组 12 只。应用TNBS乙醇灌肠诱导慢性结肠炎模型，美沙拉嗪组于诱导模型后开始每日予美沙拉嗪(5-ASA)灌胃。造模开始后14 d处死小鼠， 检测结肠组织 IFN-γ、IL-17A、IL-4和TGF-β的mRNA表达水平以及结肠组织CDC42、P38 蛋白表达水平。 结果 模型组结肠组织 CDC42，P38表达较对照组明显升高(P<0.05)，美沙拉嗪干预组较模型组表达降低(P<0.05)。模型组IFN-γ、IL-17A的mRNA表达水平较对照组明显增高(P<0.05);美沙拉嗪组较模型组表达水平下降(P<0.05)。模型组的IL-4和TGF-β表达水平较对照组升高，但差异无统计学意义(P>0.05)，美沙拉嗪组较模型组表达水平增高(P<0.05)。 结论 CDC42可能通过P38调节淋巴细胞因子的水平参与小鼠慢性结肠炎的发病。
[关键词] 慢性结肠炎;CDC42;免疫;Th1/Th2
[中图分类号] R735.3 [文献标识码] A [文章编号] 1673-9701(2019)14-0037-04
[Abstract] Objective To study the changes of CDC42 in the colon of mice with chronic colitis and its relationship with lymphocyte factor levels. Methods 36 C57BL/6 mice were randomLy divided into control group， model group and mesalazine intervention group， with 12 rats in each group. TNBS ethanol enema was used to induce chronic colitis model， and gavage administration of mesalamine(5-ASA) was performed daily after induction of the model in the mesalazine group. Mice were sacrificed at 14 days after the start of modeling. The mRNA expression levels of IFN-γ， IL-17A， IL-4 and TGF-β in colon tissues， and CDC42 and P38 protein expression levels in colon tissues were detected. Results The expression of CDC42 and P38 in the colon tissue of the model group was significantly higher than that in the control group(P<0.05)， and the expression in the mesalazine intervention group was lower than that in the model group(P<0.05). The mRNA expression levels of IFN-γ and IL-17A in the model group were significantly higher than those in the control group(P<0.05). The expression level of IFN-γ and IL-17A in mesalazine group was lower than that in the model group(P<0.05). The expression levels of IL-4 and TGF-β in the model group were higher than those in the control group， but there was no statistical significance(P>0.05). The expression level of IL-4 and TGF-βin mesalazine group was higher than that in the model group(P<0.05). Conclusion CDC42 may participate in the pathogenesis of chronic colitis in mice through P38， which regulates the level of lymphocyte factors.
[Key words] Chronic colitis; CDC42; Immunity; Th1/Th2
炎癥性肠病(inflammatory bowel disease，IBD)包括溃疡性结肠炎和克罗恩病[1]。近年国内的IBD发病率呈逐年上升趋势。IBD病因和发病机制至今尚未完全明确。目前认为免疫因素在该病发病中作用较为肯定，其中CD4+T细胞发挥了重要作用。Th1/Th2失衡一直被认为是IBD的重要因素之一[2]。Treg细胞和Th17细胞的发现成为Th1/Th2失衡学说的重要补充[2]。Thl细胞以分泌IFN-γ和IL-2为主，Th2细胞以IL-4、IL-5、IL-10为主。Th17细胞以分泌IL-17A和IL-22为主[3]，Treg细胞以分泌IL-10和TGF-β、IL-23p19为主[2]。CDC42是Rho GTP酶蛋白家族中的一员，属于细胞内信号转导因子[4]。是MAPK通路的上游信号分子[4]，有研究发现，CDC42与淋巴细胞的分化和成熟有关。本研究拟在动物水平研究慢性结肠炎发病中CDC42的可能作用及其与淋巴细胞因子的关系。, 百拇医药(董乐妹 夏芳芳 吴芳)
[关键词] 慢性结肠炎;CDC42;免疫;Th1/Th2
[中图分类号] R735.3 [文献标识码] A [文章编号] 1673-9701(2019)14-0037-04
[Abstract] Objective To study the changes of CDC42 in the colon of mice with chronic colitis and its relationship with lymphocyte factor levels. Methods 36 C57BL/6 mice were randomLy divided into control group， model group and mesalazine intervention group， with 12 rats in each group. TNBS ethanol enema was used to induce chronic colitis model， and gavage administration of mesalamine(5-ASA) was performed daily after induction of the model in the mesalazine group. Mice were sacrificed at 14 days after the start of modeling. The mRNA expression levels of IFN-γ， IL-17A， IL-4 and TGF-β in colon tissues， and CDC42 and P38 protein expression levels in colon tissues were detected. Results The expression of CDC42 and P38 in the colon tissue of the model group was significantly higher than that in the control group(P<0.05)， and the expression in the mesalazine intervention group was lower than that in the model group(P<0.05). The mRNA expression levels of IFN-γ and IL-17A in the model group were significantly higher than those in the control group(P<0.05). The expression level of IFN-γ and IL-17A in mesalazine group was lower than that in the model group(P<0.05). The expression levels of IL-4 and TGF-β in the model group were higher than those in the control group， but there was no statistical significance(P>0.05). The expression level of IL-4 and TGF-βin mesalazine group was higher than that in the model group(P<0.05). Conclusion CDC42 may participate in the pathogenesis of chronic colitis in mice through P38， which regulates the level of lymphocyte factors.
[Key words] Chronic colitis; CDC42; Immunity; Th1/Th2
炎癥性肠病(inflammatory bowel disease，IBD)包括溃疡性结肠炎和克罗恩病[1]。近年国内的IBD发病率呈逐年上升趋势。IBD病因和发病机制至今尚未完全明确。目前认为免疫因素在该病发病中作用较为肯定，其中CD4+T细胞发挥了重要作用。Th1/Th2失衡一直被认为是IBD的重要因素之一[2]。Treg细胞和Th17细胞的发现成为Th1/Th2失衡学说的重要补充[2]。Thl细胞以分泌IFN-γ和IL-2为主，Th2细胞以IL-4、IL-5、IL-10为主。Th17细胞以分泌IL-17A和IL-22为主[3]，Treg细胞以分泌IL-10和TGF-β、IL-23p19为主[2]。CDC42是Rho GTP酶蛋白家族中的一员，属于细胞内信号转导因子[4]。是MAPK通路的上游信号分子[4]，有研究发现，CDC42与淋巴细胞的分化和成熟有关。本研究拟在动物水平研究慢性结肠炎发病中CDC42的可能作用及其与淋巴细胞因子的关系。, 百拇医药(董乐妹 夏芳芳 吴芳)