1,25(OH)_2D_3在实验性溃疡性结肠炎中的作用机制  

Mechanisms underlying therapeutic effects of 1,25(OH)_2D_3 against experimental ulcerative colitis in mice

作　　者：李月芹[1] 叶建新[1] 邹玲婷[1] 张光波[1] 高楠[1] 陈卫昌[1] 

机构地区：[1]苏州大学附属第一医院消化科,江苏省苏州市215006

出　　处：《世界华人消化杂志》2013年第4期313-319,共7页World Chinese Journal of Digestology

基　　金：苏州市卫生局科教兴卫基金资助项目;No.KJXW2011001~~

摘　　要：目的:探讨1,25-二羟维生素D3[1,25(OH)2D3]在葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的小鼠溃疡性结肠炎(ulcerative colitis,UC)中的作用机制.方法:将30只Balb/c小鼠按随机数字表分为A-E组:对照组、UC组及低、中、高剂量1,25(OH)2D3干预组.A组小鼠饮用蒸馏水7d;B-E组小鼠自由饮用5%DSS溶液7d以制成UC模型.于造模第1、3、5及7天分别给C-E组小鼠以低、中、高剂量1,25(OH)2D3(50、100、200ng/只)腹腔内注射,A-B组予腹腔注射溶药载体无菌大豆油作为对照.观察指标包括疾病活动指数(disease activity index,DAI)和结肠组织病理学评分(histopathological score,HPS).于造模第8天,处死所有小鼠.应用免疫组织化学方法测定小鼠结肠干扰素-γ(interferon-γ,IFN-γ)、白介素(interleukin,IL)-17和IL-4蛋白水平的表达.结果:(1)与对照组DAI和HPS相比,模型组小鼠DAI和HPS明显增高(7.33±1.03 vs 0.33±0.52,12.00±0.63 vs 0.17±0.41,P<0.01);与模型组相比,经1,25(OH)2D3干预后C-E组DAI(2.83±0.40、2.83±0.75、2.33±0.52)和HPS(10.83±0.98、7.50±0.84、6.67±0.52)均有不同程度的下降(P<0.01);(2)模型组小鼠结肠IFN-γ(548.00±36.25)和IL-17(121.48±12.34)的表达显著高于对照组IFN-γ(76.68±14.19)和IL-17(31.89±4.19)(P<0.01),干预组IFN-γ(252.82±32.06、141.72±21.07、171.70±17.12)和IL-17(76.86±4.48、47.00±6.64、37.54±5.36)的表达明显低于模型组(P<0.01);模型组IL-4(49.72±11.08)的表达则显著低于对照组(89.83±6.97)(P<0.01),干预组IL-4(127.23±11.04、303.82±78.14、185.31±19.01)的表达明显高于模型组(P<0.01).结论:1,25(OH)2D3有助于维持结肠黏膜的局部免疫平衡机制,减轻溃疡性结肠炎的炎症.AIM：To explore the mechanisms underlying the therapeutic effects of 1,25-dihydroxyvitamin D3 [1,25（OH）2D3] against experimental ulcerative colitis（UC）.METHODS：Thirty Balb/c mice were randomly assigned to groups A to E：control group,model group,low-,medium-,and high-dose intervention groups.Groups B-E were given 5% DSS solution for seven days to induce UC,while group A was given equal volume of distilled water.On days 1,3,5,and 7,groups C-E were intraperitoneally injected with 50,100 and 200 ng of 1,25（OH）2D3,respectively.Disease activity index（DAI） and histopathological score（HPS） were calculated.The protein expression of interferon-γ（IFN-γ）,inter leukin（IL）-17 and IL-4 in colonic tissues was measured by immunohistochemistry.RESULTS：Compared to the control group,the DAI and HPS were significantly higher in the model group（7.33±1.03 vs 0.33±0.52,12.00 ±0.63 vs 0.17±0.41,both P0.01）.Compared to the model group,the DAI（2.83±0.40,2.83±0.75,2.33±0.52） and HPS（10.83±0.98,7.50±0.84,6.67±0.52） significantly decreased in the three intervention groups（all P0.01）.The expression of IFN-γ and IL-17 was significantly higher in the model group than in the control group（both P0.01）,and was significantly lower in the intervention groups than in the model group（all P0.01）.IL-4 expression was significantly lower in the model group than in the control group（P0.01）,and was significantly higher in the intervention group than in the model group（P0.01）.CONCLUSION：1,25（OH）2D3 can maintain local immune balance in the colonic mucosa and reduce inFLammation in ulcerative colitis.

关 键 词：1 25-二羟维生素D3 溃疡性结肠炎 干扰素-Γ 白介素17 白介素4 

分 类 号：R574.62[医药卫生—消化系统]