TL1A通过调控IL-17和IFN-γ促进慢性实验性结肠炎相关肠纤维化的发生  

TL1A promotes development of intestinal fibrosis associated with chronic experimental colitis by regulating IL-17 and IFN-γ

作　　者：尹凤荣[1] 战蓉蓉 王冬[1] 宋佳[1] 李辉[1] 张红[1] 张晓岚[1] YIN Feng-rong;ZHAN Rong-rong;WANG Dong;SONG Jia;LI Hui;ZHANG Hong;ZHANG Xiao-lan(Department of Gastroentology,The Second Hospital of Hebei Medical University,Hebei Key Laboratory of Gastroenterolo⁃gy,Hebei Institute of Gastroenterology,Shijiazhuang 050035,China)

机构地区：[1]河北医科大学第二医院消化内科,河北省消化病重点实验室,河北省消化病研究所,河北石家庄050035

出　　处：《中国病理生理杂志》2020年第6期1096-1103,共8页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81370501)。

摘　　要：目的:探讨肿瘤坏死因子配体1A(TL1A)通过调控白细胞介素17(IL-17)和干扰素γ(IFN-γ)促进慢性实验性结肠炎相关肠纤维化的发生。方法:建立葡聚糖硫酸钠(DSS)诱导的慢性实验性结肠炎相关野生型及TL1A(L-Tg)转基因型肠纤维化模型,通过疾病活动指数(DAI)评分、HE染色及髓过氧化物酶(MPO)含量评估结肠炎症程度,马松染色和天狼星红染色评估肠纤维化程度,流式细胞术检测脾和淋巴结单个核细胞中CD4^+IFN-γ^+和CD4^+IL-17^+细胞的比例,ELISA测定上述细胞IL-17和IFN-γ的分泌水平。结果:与野生型小鼠相比,转基因小鼠的体重下降更明显,DAI评分、病理学评分和结肠组织MPO含量均显著增高,且马松染色和天狼星红染色提示纤维化程度加重;流式细胞术检测脾脏和淋巴结单个核细胞中的CD4^+IFN-γ^+T细胞和CD4^+IL-17^+T细胞的比例也明显升高;ELISA测定脾、淋巴结及肠黏膜固有层单个核细胞分泌IL-17和IFN-γ的水平显著升高(P<0. 05)。结论:TL1A通过调控IL-17和IFN-γ促进慢性实验性结肠炎相关肠纤维化的发生。AIM:To explore how tumor recrosis factor ligand-related molecule 1A(TL1A)promotes the de⁃velopment of intestinal fibrosis associated with chronic experimental colitis by regulating interleukin-17(IL-17)and inter⁃feron-γ(IFN-γ).METHODS:Aexperimental colitis-associated wild-type(WT)and TL1A(L-Tg)transgenic intestinal fibrosis model was established by dextran sulfate sodium(DSS)induction.The severity of colitis was evaluated by detect⁃ing the disease activity index(DAI).HE staining was used to observe the histopathological changes and pathological score of the colitis.Myeloperoxidase(MPO)was measured in each group.The collagen deposition was detected by Masson’s tri⁃chrome staining and Sirius red staining.The lamina propria,spleen and mesenteric lymph nodes(MLN)mononuclear cells were isolated and counted,and the levels of IL-17 and IFN-γweremeasured by ELISA,andthe percentages of CD4+IFN-γ+T cells and CD4+IL-17+T cells were analyzed by flow cytometry.RESULTS:After drinking DSS water,the body weight of the mice in DSS/Tg group was decreased significantly as compared with WT group(P<0.05).The DAI score,histology score and MPO activity were significantly increased(P<0.05).Thelevels of IL-17 and IFN-γ,LPMC,spleen and MLN were significantly increased.The percentages of CD4+IFN-γ+T cells and CD4+IL-17+T cells were signifi⁃cantlyincreased.The thickness and collagen deposition of the colon were increased inTg group.CONCLUSION:TL1A promotes the development of intestinal fibrosis associated with chronic experimental colitis by regulating IL-17 and IFN-γ.

关 键 词：炎症性肠病 肠纤维化 干扰素Γ 白细胞介素17 肿瘤坏死因子样配体1A 

分 类 号：R574.62[医药卫生—消化系统] R363.2[医药卫生—内科学]