1,25-二羟基维生素D_3对溃疡性结肠炎小鼠免疫调节机制的研究

The effects of 1,25-dihydroxyvitamin D_3 on the immunologic mechanism of IL-23/IL-17 in the experimental colitis

目的探讨1,25-二羟基维生素D_3[1,25(OH)_2D_3]对溃疡性结肠炎模型小鼠IL-23/IL-17的免疫调节机制。方法 2009年1—12月在河北中医药研究所,将30只小鼠随机分为1,25(OH)_2D_3干预组、模型组、对照组,前2组建立慢性期肠炎模型;观察小鼠一般情况及结肠病理变化,应用免疫组织化学染色测定结肠组织TNF-α、TGF-β炎性因子的变化;Western blot检测结肠组织IL-17、IL-23蛋白的表达。结果模型组小鼠结肠黏膜缺损,腺体破坏或消失,显微镜下可见黏膜、黏膜下层甚至肌层大量炎性细胞浸润;但1,25(OH)_2D_3干预后小鼠一般情况明显改善,炎性细胞浸润减少,炎性反应程度较模型组明显减轻;与模型组比较,干预组结肠组织TNF-α、TGF-β阳性细胞染色面积明显减小(F=280.48、358.75,P<0.01),结肠组织中IL-17、IL-23蛋白表达量显著降低(F=1 447.52、1457.57,P<0.01)。结论 1,25(OH)_2D_3对溃疡性结肠炎模型小鼠的肠黏膜组织及其IL-23/IL-17具有免疫调节作用。

Objective To investigate the effects of 1,25（OH）2D3 on the immunologic mechanism of IL-23/IL-17 in chronic colitis mice.Methods Thirty of mice were randomly grouped as follows;1,25（OH）2D3 group,model group,control group.Chronic colitis model was established,general condition and colon pathological changes were observed.The expressions of TNF-a and TGF-β proteins were detected by immunohistochemistry,and the expressions of IL-17,IL-23 proteins were detected by western blot.Results During the experiment,general condition and colon pathological were changed in the 1,25（OH）2D3 group compared with that of the model group,infiltration into the mucosa superficial layers of granulocytes,neutrophil infiltration of rectum were much severity in the model group by the microscope.However,mice in the 1,25（OH）2D3group,the colonic pathological section showed increased,neutrophils were significantly ameliorated;the results of immunohistochemical staining showed that the expressions of the TNF-a and TGF-β proteins in colonic tissues significantly decreased in the 1,25（OH）2D3 group compared with that of the model group（P 〈0.01）,the results of western blot revealed that the proteins expressions of IL-17,IL-23 significantly decreased in the 1,25（OH）2D3 group compared with that of the model group（F = 1 447.52,P 〈0.01;F = 1 457.57,P 〈0.01）.Conclusion The administration of 1,25（OH）2D3 could relieve the damages of chronic colitis in mice,which may be adjusted the immunologic mechanism of IL-23/IL-17 in intestinal tissues.