姜黄素通过IL-6/STAT3信号通路调控Th17/Treg平衡治疗溃疡性结肠炎

Curcumin regulates Th17/Treg balance in treatment of ulcerative colitis by IL-6/STAT3 signaling pathway

目的:观察姜黄素对溃疡性结肠炎(UC)模型小鼠的疗效及对IL-6/STAT3信号通路中相关分子表达和结肠组织中Treg、Th17细胞水平的影响,探究姜黄素是否通过IL-6/STAT3信号通路调控Th17/Treg平衡以有效治疗UC。方法:采用葡聚糖硫酸钠(DSS)制备UC小鼠模型,将50只健康雌性BALB/c小鼠随机分为5组:正常对照组,UC模型组及姜黄素低、中、高剂量组。HE染色观察小鼠结肠黏膜组织损伤程度并评分,Western blot检测结肠组织中IL-6、STAT3及p-STAT3的蛋白水平,流式细胞术分析结肠组织中Treg和Th17细胞的水平,Western blot检测结肠组织中Treg转录因子FOXP3和Th17转录因子RORγt的表达情况。结果:UC小鼠结肠部位溃疡形成,镜下可见炎症和充血等病理改变,姜黄素中剂量组的黏膜损伤基本恢复正常,只有少量炎性细胞。与正常组相比,UC小鼠结肠组织IL-6、STAT3和p-STAT3的蛋白水平均显著增高;与模型组相比,姜黄素中剂量组IL-6、STAT3和p-STAT3的蛋白水平均明显降低,接近正常组,并且中剂量姜黄素能显著降低Th17细胞的水平和转录因子RORγt的表达,而显著升高Treg细胞的水平和转录因子FOXP3的表达。姜黄素低剂量组和高剂量组对上述指标均无明显影响。结论:姜黄素可以有效治疗DSS诱导的小鼠UC,其作用机制可能是通过IL-6/STAT3信号通路来调控Th17/Treg平衡。

AIM: To observe the curative effect of curcumin on ulcerative colitis(UC) model mice, expression of related molecules in IL-6/STAT3 signaling pathway and the levels of Treg and Th17 cells in colon tissue, and to explore whether curcumin regulates Th17/Treg balance through IL-6/STAT3 signaling pathway to effectively treat UC. METHODS: Healthy female BALB/c mice(n=50) were randomly divided into 5 groups: normal control group, UC model [induced by dextran sulfate sodium(DSS)] group, and low-, medium-and high-dose curcumin groups. The damage degree of colonic mucosa in the mice was observed and scored. The protein levels of IL-6, STAT3 and p-STAT3 were determined by Western blot. The levels of Treg and Th17 cells were analyzed by flow cytometry. The Treg transcription factor FOXP3 and Th17 transcription factor RORγt were detected by Western blot. RESULTS: Ulceration of colon, and pa-thological changes such as inflammation and congestion were observed under microscope in the UC mice. The mucosal da-mage in curcumin(medium dose) group was basically normal, and only a small amount of inflammatory cells was found. Compared with normal group, the protein levels of IL-6, STAT3 and p-STAT3 in the colon tissue of UC mice were significantly increased(P<0.05). Compared with model group, the protein levels of IL-6, STAT3 and p-STAT3 in medium dose of curcumin group were decreased significantly, and were close to those in control group. The medium dose of curcumin significantly reduced the levels of Th17 cells and the transcription factor RORγt, but significantly increased the levels of Treg cells and the transcription factor FOXP3. Curcumin at low dose and high dose had no significant effect on the above indexes. CONCLUSION: Curcumin effectively attenuates the mucosal damage of the mice with DSS-induced UC, and the mechanism may be related to regulating Th17/Treg balance through IL-6/STAT3 signaling pathway.