上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2020, Vol. 40 ›› Issue (3): 286-.doi: 10.3969/j.issn.1674-8115.2020.03.003

• 创新团队成果专栏 • 上一篇    下一篇

CD8+ T细胞在葡聚糖硫酸钠诱导的小鼠急性结肠炎中的致病性研究

曾群雄1, 2，邓 军1, 2，沈 南1, 2   

  1. 1. 上海交通大学医学院附属仁济医院，上海市风湿病学研究所，上海200127；2.上海交通大学医学院附属仁济医院中澳个体化自身免疫病研究中心，上海200127
  • 出版日期:2020-03-28 发布日期:2020-04-09
  • 通讯作者: 沈 南，电子信箱：nanshensibs@gmail.com。
  • 作者简介:曾群雄（1992—），男，硕士生；电子信箱：zengqunxiong@icloud.com。
  • 基金资助:
    国家自然科学基金（31600708, 81974252, 81421001, 81571575, 81771737）；上海交通大学医学院高水平地方高校创新团队（SSMU-ZDCX20180100）。

Pathogenesis of CD8+ T cells in dextran sulfate sodium-induced murine acute colitis

ZENG Qun-xiong, DENG Jun, SHEN Nan   

  1. 1. Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China; 2. China-Australia Centre for Personalized Immunology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China
  • Online:2020-03-28 Published:2020-04-09
  • Supported by:
    National Natural Science Foundation of China (31600708, 81974252, 81421001, 81571575, 81771737); Innovative Research Team of High-Level Local Universities in Shanghai (SSMU-ZDCX20180100).

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摘要： 目的·通过葡聚糖硫酸钠（dextran sulfate sodium，DSS）诱导的小鼠急性结肠炎模型，观察CD8+ T细胞在小鼠急性结肠炎发病中的作用。方法·给予野生型C57BL/6小鼠和CD8敲除（CD8-/-）小鼠饮用质量浓度为2%的DSS溶液诱导急性结肠炎模型，观察体质量动态变化、结肠长度及病理改变、肠炎疾病活动度变化。诱导10 d后收集小鼠远端结肠，抽提总RNA，采用实时荧光定量PCR检测肠炎小鼠结肠组织中炎症细胞因子Il1b、Il6、Il17a、Ifng、Tnf、Il10和Tgfb1 mRNA表达水平。通过苏木精 - 伊红（H-E）染色评估结肠组织病理学改变，通过免疫荧光染色观察结肠组织中CD8+ T细胞的浸润情况。采用质量浓度为3%和4%的DSS溶液诱导肠炎后观察小鼠存活率。结果·2%DSS诱导急性结肠炎后，CD8-/-小鼠体质量下降速度较慢，在第9日呈现上升趋势，CD8-/-小鼠结肠组织病理改变较轻；与野生型小鼠比较，CD8-/-小鼠结肠中促炎症细胞因子Il1b、Il6、Il17a、Ifng 和Tnf mRNA表达水平较低（均P+ T细胞，与未造模小鼠的差异具有统计学意义（P0.001）。经3%和4% DSS诱导急性结肠炎后，WT小鼠存活率为37.5％和0，CD8-/-小鼠存活率为66.7％和100%；与WT小鼠比较，CD8-/-小鼠存活率高（P0.025，P0.001） 。结论·CD8+ T细胞促进DSS诱导的小鼠急性结肠炎的发生。

关键词: CD8+ T细胞, 葡聚糖硫酸钠, 急性结肠炎, 致病性, 小鼠

Abstract:

Objective · To investigate the role of CD8+ T cells in the pathogenesis of acute murine colitis induceddextran sulfate sodium (DSS). Methods · Wild type and CD8 knock-out (CD8-/-) mice with C57BL/6 background were given DSS with concentration of 2% (m/V). The body weight, colon length, pathological changes and disease activity of colitis were observed dynamically. The total RNA was extracted the distal colon of mice after induction for 10 d. The mRNA of inflammatory cytokines Il1b, Il6, Il17a, Ifng, Tnf, Il10 and Tgfb1 were detectedreal-time quantitative PCR. Colon tissue sections were stained with hematoxylin-eosin (H-E) and the changes of intestinal histopathology were evaluated, and the infiltration of CD8+ T cells in colon tissue was observedimmunofluorescence staining. The survival rate of mice was observed with 3% and 4% (m/V) DSS solution-induced colitis models. Results · After CD8-/- mice being induced2% DSS, the body weight decreased slowly and showed an increasing trend on the 9th day, while the pathological changes of colon tissues of CD8-/- mice were slight. The levels of Il1b, Il6, Il17a, Ifng and Tnf mRNA were lower than those of wild-type mice (P+ T cells in colonic lamina propria of wild-type mice with 2% DSS induction was higher than that of wild-type mice without DSS treatment (P0.001). The survival rates of wild-type mice induced3% and 4% DSS were 37.5% and 0, and the survival rates of CD8-/- mice were 66.7% and 100%, while the survival rates of CD8-/- mice receiving 3% and 4% DSS were higher than those of wild-type mice (P0.025, P0.001). Conclusion · CD8+ T cells can promote the development of murine acute DSS-induced colitis.

Key words: CD8+ T cells, dextran sulfate sodium, acute colitis, pathogenesis, mouse