目的 探讨在炎症性肠病(IBD)中姜黄素的疗效和潜在的作用机制.方法 由30 g/L葡聚糖硫酸钠(DSS)诱导幼年大鼠溃疡性结肠炎模型,24只幼鼠分为4组:正常组、模型组、姜黄素100 mg/kg组(姜黄素100组)、姜黄素300 mg/kg组(姜黄素300组),姜黄素灌胃每天1次,连续灌胃7 d.观察幼鼠的一般情况、疾病活动指数(DAI)和病理组织学评分,采用流式细胞术检测幼鼠脾脏CD4+ CD25+ Foxp3+调节性T淋巴细胞(Treg)和CD4+ IL-17+辅助性T淋巴细胞17(Th17)占CD4+ T淋巴细胞的百分比,采用免疫组织化学法检测SOCS3表达水平.结果 在给药第5天时,与模型组[(7.50±0.32)分]相比,姜黄素100组[(4.00±1.10)分]、姜黄素300组[(5.00±0.89)分]DAI评分明显降低,差异有统计学意义(F=12.469,P<0.05);在给药第7天后,姜黄素100组[(1.94±0.68)分]、姜黄素300组[(2.00±0.63)分]、正常组[(0.50±0.05)分]组织学评分显著低于模型组[(2.69±0.70)分],差异有统计学意义(F=33.282,P<0.05).姜黄素100组[(0.002 0±0.000 5)D]、姜黄素300组[(0.002 6±0.006 0)D]、正常组[(0.002 2±0.001 0)D]SOCS3表达显著低于模型组[(0.015 1±0.000 7)D],差异有统计学意义(F=382.270,P<0.05),但前三者间差异无统计学意义(F=0.828,P>0.05).在CD4+ CD25+ Foxp3+ Treg的比例上,姜黄素100组[(9.9±1.0)%]、姜黄素300组[(9.3±0.7)%]、正常组[(9.6±1.1)%]较模型组[(6.5±1.5)%]明显升高,差异有统计学意义(F=16.635,P<0.05),但前三者间差异无统计学意义(F=1.564,P>0.05).在CD4+ IL-17+ Th17的比例上,姜黄素100组[(2.0±0.9)%]、姜黄素300组[(1.2±0.6)%]、正常组[(2.0±0.9)%]较模型组[(3.5±1.4)%]显著降低,差异有统计学意义(F=5.155,P<0.05),但是前三者间差异无统计学意义(F=2.073,P>0.05).上述指标在姜黄素100组、姜黄素300组间差异均无统计学意义(均P>0.05).结论 姜黄素可能通过减少SOCS3的表达来调节Treg/Th17的平衡,从而缓解实验性IBD的严重程度和减轻炎性反应.%Objective To determine the therapeutic efficacy of curcumine on inflammatory bowel disease(IBD)and its underlying mechanisms.Methods The rat ulcerative colitis model was developed by using 30 g/L dextran sulfate sodium.Twenty-four young rats were divided into 4 groups:normal group,model group,curcumin 100 mg/kg group(curcumin 100 group),and curcumin 300 mg/kg group(curcumin 300 group).Curcumin was given through gastric gavage once a day for 7 days.General condition,disease activity index(DAI)and histopathological score(HPS)were evaluated.The proportions of CD4+ CD25+ Foxp3+ regulatory T cells(Treg)and CD4+ IL-17+ helper T lymphocyte 17(Th17)in CD4+ T cells in rats,and spleen cells were calculated by using flow cytometry.Immunohistochemical method was performed to determine the level of SOCS3 in colon tissues.Results After curcumin administered through gastric gavage for 5 days,compared with the DAI in the model group[(7.50±0.32)scores],HPS in the curcumin 100 group[(4.00±1.10)scores] and the curcumin 300 group [(5.00±0.89)scores] significantly reduced,and the difference was significant(F=12.469,P<0.05).After curcumin administered through gastric gavage for 7 days,compared with the HPS in the model group[(2.69±0.70)scores],histological score in the curcumin 100 group[(1.94±0.68)scores],the curcumin 300 group [(2.00±0.63)scores] and the normal group[(0.50±0.05)scores] significantly reduced,and the difference was significant(F=33.282,P<0.05).Compared with the model group[(0.015 1±0.000 7)D],the expression of SOCS3 in the curcumin 100 group[(0.002 0±0.000 5)D],the curcumin 300 group [(0.002 6±0.006 0)D] and the normal group[(0.002 2±0.001 0)D] was significantly inhibited(F=382.270,P<0.05),but there was no difference among the former 3 groups(F=0.828,P>0.05).Compared with the model group[(6.5±1.5)％],the propotion of CD4+ CD25+ Foxp3+ Treg cells in CD4+ T cells in the curcumin 100 group[(9.9±1.0)％],the curcumin 300 group [(9.3±0.7)％] and the normal group[(9.6±1.1)％]was obviously upregulated(F=16.635,P<0.05),but there was no difference among the former 3 group(F=1.564,P>0.05).Compared with the model group[(3.5±1.4)％],the propotion of CD4+ IL-17+ Th17 cells in CD4+ T cells in the curcumin 100 group[(2.0±0.9)％],the curcumin 300 group [(1.2±0.6)％] and the normal group[(2.0±0.9)％] was downregulated(F=5.155,P<0.05),but there was no difference among the former 3 group(F=2.073,P>0.05).There was no obvious difference between the curcumin 100 group and the curcumin 300 group in these indicators respectively(all P>0.05).Conclusions Curcumin probably attenuates IBD severity,reduces inflammation and regulates the balance of Treg/Th17 through the inhibition of SOCS3 expression.
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