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目的研究丁酸钠对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠结肠组织辅助性T细胞(Th)1、Th2和Th17类细胞因子平衡的影响。方法 80只雄性Balb/c小鼠随机分成4组:正常组、模型组、空白组、实验组,正常组饮水,另外3组给予4.5%DSS连续7 d,建立结肠炎模型。空白组给予生理盐水,实验组每日1次灌胃丁酸钠0.2 m L连续7 d。监测各组的小鼠体重、生存情况、结肠长度变化,以HE染色观察结肠组织病理改变,以酶联免疫吸附法检测小鼠结肠组织Th2类细胞因子[白细胞介素(IL)IL-4、IL-6、IL-10]、Th1类细胞因子[肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)]及Th17细胞因子(IL-17)的表达情况。结果造模第7天与正常组比较,模型组体重显著降低(P<0.001),结肠长度显著缩短(P<0.05),结肠组织IL-4、IL-6、IL-10、TNF-α、IFN-γ、IL-17表达均增高。干预后第7天与空白组比较,实验组的体重明显升高(P<0.05),结肠明显伸长(P<0.05),生存率明显增高(50%vs 70%),实验组的IL-4、IL-6、IL-10、TNF-α、IFN-γ、IL-17均较空白组明显降低:(367.89±29.83)vs(693.49±228.77)pg·m L~(-1),(256.29±34.18)vs(704.49±179.00)pg·m L~(-1),(392.44±28.70)vs(992.34±159.93)pg·m L~(-1),(361.81±63.39)vs(816.31±204.00)pg·m L~(-1),(302.43±42.59)vs(527.58±152.27)pg·m L~(-1),(250.10±36.15)vs(400.16±118.28)pg·m L~(-1)(均P<0.05);实验组各细胞因子均接近正常组水平,与正常组的比值:IL-4为1.94,IL-6为1.51,IL-10为1.62,TNF-α为1.13,IFN-γ为1.34,IL-17为1.31。病理等级评估,模型组均为Ⅱ级以上;经丁酸钠干预后,实验组明显优于空白组,2组分别有71.0%,38.5%降为Ⅱ级以下。结论丁酸钠通过促进Th1/Th2/Th17类细胞因子平衡发挥促进结肠炎缓解的作用。
Objective To investigate the effect of sodium butyrate on the balance of helper T cell (Th) 1, Th2 and Th17 cytokines in colon of mice with dextran sulfate sodium (DSS) -induced colitis. Methods Eighty male Balb / c mice were randomly divided into 4 groups: normal group, model group, blank group, experimental group and normal group. The other 3 groups were given 4.5% DSS for 7 consecutive days to establish colitis model. The rats in the blank group were given normal saline, while the experimental group was given 0.2 mg sodium butyrate once daily for 7 days. The body weight, survival and colonic length of the mice in each group were observed. The pathological changes of colonic tissue were observed by HE staining. Th2 cytokines (interleukin (IL) IL-4, IL-6, IL-10] and Th1 cytokines such as tumor necrosis factor-α (TNF-α), interferon-γ (IFN- γ) and Th17 cytokines (IL-17) Results Compared with the normal group, the body weight of the model group was significantly decreased (P <0.001) and the length of the colon was significantly shortened (P <0.05) on the 7th day. The expressions of IL-4, IL-6, IL-10, TNF- IFN-γ, IL-17 expression were increased. At 7 days after intervention, the body weight of the experimental group was significantly increased (P <0.05), the colon was significantly longer (P <0.05) and the survival rate was significantly higher (50% vs 70%) than that of the blank group. The IL- (367.89 ± 29.83) vs (693.49 ± 228.77) pg · m L -1, (P <0.05), the level of IL-6, IL-10, TNF-α, IFN-γ and IL- 256.29 ± 34.18) vs (704.49 ± 179.00) pg · m L -1, (392.44 ± 28.70) vs (992.34 ± 159.93) pg · m L -1, (361.81 ± 63.39) vs (816.31 ± 204.00) pg · m L -1, (302.43 ± 42.59) vs (527.58 ± 152.27) pg · m L -1, (250.10 ± 36.15) vs (400.16 ± 118.28) pg · m L ~ -1) (all P <0.05). The ratio of cytokines in the experimental group was close to that of the normal group, the ratio of the cytokine to the normal group was 1.94 for IL-4, 1.51 for IL-6, 1.62 for IL-10 and 1.13 for TNF- , IFN-γ was 1.34 and IL-17 was 1.31. Pathological grade assessment, model group were grade Ⅱ above; after sodium butyrate intervention, the experimental group was significantly better than the blank group, 71.0% in the two groups, 38.5% down to Ⅱ grade. Conclusion Sodium butyrate can promote colitis remission by promoting the balance of Th1 / Th2 / Th17 cytokines.