IL-17和Foxp3在小鼠克罗恩病模型中的表达及其意义  

Expression and Significance of IL-17 and Foxp3 in the Crohn Mouse Model

作　　者：曾放[1] 孙华文[1] 刘顺[1] 孙科明 吴红学[1] 

机构地区：[1]武汉大学人民医院胃肠外科,武汉430060

出　　处：《医学综述》2016年第9期1751-1754,F0003,共5页Medical Recapitulate

基　　金：国家自然科学基金(81170368)

摘　　要：目的观察小鼠克罗恩病模型外周血单核细胞及结肠组织中白细胞介素（IL）17、叉头状/翅状螺旋蛋白3（Foxp3）的表达,探讨其在2,4,6-三硝基苯磺酸（TNBS）诱导的克罗恩病小鼠急性炎症中的作用。方法共40只6~8周龄雌性Bal/c小鼠,采用随机数字表法随机分为两组,20只以TNBS/乙醇溶液灌肠诱导克罗恩病模型（实验组）,另外20只小鼠以同等浓度的乙醇氯化钠灌肠（正常对照组）。干预1周后行疾病活动指数（DAI）,结肠病理组织学评分（TDI）和结肠大体形态损伤指数（CMDI）评价,以实时荧光定量反转录聚合酶链反应（RT-PCR）检测小鼠外周血单核细胞IL-17mRNA、Foxp3 mRNA的表达,采用免疫印迹法检测小鼠结肠组织IL-17蛋白、Foxp3蛋白的表达。结果与正常对照组相比,实验组的DAI、TDI、CMDI显著升高[DAI（5.41±0.48）比（0.85±0.07）,TDI（5.63±0.74）比（0.74±0.08）,CMDI（6.88±0.84）比（0.91±0.06）,P〈0.01],外周血单核细胞的IL-17 mRNA显著升高[（1.118±0.145）比（1.000±0.000）,P〈0.01],与其DAI、TDI及CMDI呈正相关（r=0.875,0.935,0.825,P〈0.01）,Foxp3 mRNA显著降低[（0.797±0.271）比（1.000±0.000）,P〈0.01],与其DAI、TDI及CMDI呈负相关（r=-0.885,-0.734,r-0.812,P〈0.01）,结肠组织IL-17蛋白显著上升[（0.631±0.331）比（0.272±0.112）,P〈0.01],与其DAI、TDI及CMDI呈正相关（r=0.765,0.778,0.734,P〈0.01）,Foxp3蛋白显著降低[（0.274±0.112）比（0.592±0212）,P〈0.01],与DAI、TDI及CMDI呈负相关（r=-0.889,-0.809,-0.851,P〈0.01）。结论在TNBS诱导的结肠炎中,Th17/Treg轴的免疫偏倚是导致克罗恩病发生和发展的重要因素。Objective To observe the expression of interleukin （IL） -17 and forkhead/winged helix pro- tein 3 （ Foxp3 ） in the peripheral blood and colon on Crohn disease mice model, and explore their role in the process of Crohn＇s disease induced by TNBS. Methods Total of 20 Crohn disease model mice were induced by TNBS/ethanol solution, another 20 mice receiving 50% ethanol served as normal control. After one week, the disease activity index（DAD ,tissue damage index（TDI） and colon macroscopic damage iudex（CMDI） were evaluated, the level of IL-17 mRNA, Foxp3 mRNA peripheral blood monocytes were determined by RT-PCR,and the colonic expression of IL-17 protein and Foxp3 protein were determined by Western-bolt （WB）. Results Compared with normal control group, DAI,TDI and CMDI of model group were increased significantly[ DAI（5. 41±0. 48） vs （0.85 ±0.07） ,TDI（5.63 ±0. 74） vs （0. 74 ±0. 08） ,CMDI（6. 88 ±0. 84 ） vs （0. 91 ±0. 06 ） ,P 〈 0. 01 ], the level of IL-17 roRNA in peripheral blood monocytes were increased significantly [ （ 1.118 ± 0. 145 ） vs （ 1. 000 ± 0. 000）, P 〈 0.01 ], and was positively correlated with DAI, TDI and CMDI （ r =0. 875,0. 935,0. 825, P 〈 O. 01 ） ; Foxp3 mRNA significantly decreased [ （ 0. 797 ±0. 271 ） vs （ 1. 000 ±0. 0013 ）, P 〈 0. 01 ], and was negatively correlated with DAI, TDI and CMDI （ r = - 0. 885, -0. 734, - 0. 812, P 〈 0. 01 ） ; the colonic expression of IL-17 and Foxp3 greatly increased [ （0. 631 ± 0. 331 ） vs （0. 272±0. 112 ）, P 〈 0. 01 ], and was positively correlated with DAI, TDI and CMDI （ r = 0. 765,0. 778,0. 734,P 〈 0. 01 ） ; Foxp3 significantly decreased [ （ 0. 274±0. 112 ） vs （0. 592 ± 0212 ）, P 〈0. 01 ] ,and was negatively correlated with DAI,TDI and CMDI（r = -0. 889, -0. 809, -0. 851 ,P 〈 0.01 ）. Conclusion The immune bias of Thl7/Tery axis plays an important role in the process of TNBS- induced Crohn disease.

关 键 词：克罗恩病 白细胞介素17 叉头状/翅状螺旋蛋白3 免疫偏倚 

分 类 号：R392.12[医药卫生—免疫学]