姜黄素对溃疡性结肠炎小鼠Th17细胞分化相关因子表达水平的影响

Effect of Curcumin on Expression of Differentiation-related Factors in Th17 in Mice with Ulcerative Colitis

关键词:  姜黄素  溃疡性结肠炎  细胞因子  信号通路因子  辅助性T细胞17

Key words:  curcumin  ulcerative colitis  cytokine  signaling pathway factor  T helper cell 17(Th17)

摘要:

目的 研究姜黄素对溃疡性结肠炎（ulcerative colitis，UC）小鼠辅助性T细胞17（T helper cell 17，Th17）分化相关因子表达的影响，探讨其治疗UC的潜在机制。方法 50只SPF级BALB/c小鼠随机分为空白对照组、模型对照组、柳氮磺胺吡啶组、姜黄素低剂量组、姜黄素高剂量组，每组10只。右旋葡聚糖硫酸钠（dextran sulphate sodium，DSS）诱导法建立溃疡性结肠炎小鼠模型并鉴定，每天灌胃给药1次，连续7 d。记录小鼠临床症状，行疾病活动度指数（disease activity index，DAI）评分，末次给药后处死小鼠，行结肠大体形态损伤指数（colon macroscopic damage index，CMDI）评分，光镜下观察结肠组织的病理学变化，并评估组织损伤指数（tissue damage index，TDI），ELISA法检测小鼠结肠组织中白介素6（interleukin 6，IL-6）、白介素17（interleukin 17，IL-17）、β转化生长因子（transforming growth factor β，TGF-β）的表达水平，Western blotting检测小鼠结肠组织中维甲酸相关孤儿核受体gt（retinoid-related orphan receptors γt，RORγt）、信号传导及转录激活因子3（signal transducers and activators of transcription，STAT3）和磷酸化STAT3（p-STAT3）的蛋白表达。结果 与空白对照组相比，模型对照组小鼠DAI、CMDI、TDI评分显著上升，IL-6、RORγt、STAT3、p-STAT3、IL-17表达水平均显著上升，TGF-β表达水平显著下降，差异均有统计学意义（P<0.01）。与模型对照组比，姜黄素治疗组中小鼠DAI、CMDI、TDI评分显著下降，IL-6、RORγt、STAT3、p-STAT3、IL-17表达水平均显著下降，TGF-β表达水平显著上升，差异均有统计学意义（P<0.05或P<0.01）。结论 姜黄素可以改善UC小鼠的临床症状，减轻结肠组织损伤，其治疗UC的机制可能与调节Th17分化功能有关。

Abstract:

OBJECTIVE To observe the effect of curcumin on the expression of differentiation-related factors of T helper cell 17 (Th17) in mice with ulcerative colitis, exploring the potential mechanism of curcumin in the treatment of ulcerative colitis(UC). METHODS Fifty SPF grade BALB/c mice were randomly divided into five groups:blank control group, model group, curcumin low-dose group, curcumin high-dose group and sulfasalazine control group, 10 mice in each group. UC model was established by dextran sulphate sodium(DSS), then daily by means of intragastric administration for 7 d. During the course of experiment, the clinical symptoms of mice were recorded, and the disease activity index (DAI) score was recorded. At the end of the experiment, the mice were sacrificed, and the colon macroscopic damage index (CMDI) was scored. The pathological changes of colon tissue were observed under microscope and the tissue damage index (TDI) was evaluated. The expression levels of IL-6, IL-17 and TGF-b in colon tissues of mice were detected by ELISA. And the expression levels of retinoid-related orphan receptors gt (RORgt) and phosphorylated STAT3 (p-STAT3) in colon tissues of mice were detected by Western blotting. RESULTS Compared with the normal control group, the scores of DAI, CMDI and TDI in model group increased significantly(P<0.01), the expression level of TGF-β decreased significantly(P<0.01), the expression levels of IL-6, IL-17, RORγt, STAT3, p-STAT3 increased significantly(P<0.01). Compared with the model group, the scores of DAI, CMDI and TDI in curcumin treatment group decreased significantly(P<0.05 or P<0.01), the expression level of TGF-β increased significantly(P<0.05 or P<0.01), the expression levels of IL-6, IL-17, RORγt, STAT3, p-STAT3 decreased significantly(P<0.05 or P<0.01). CONCLUSION Curcumin can improve the clinical symptoms of UC mice and alleviate the damage of colon tissue. The mechanism of curcumin in treating UC may be related to regulating the differentiation function of Th17 cells.