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目的探讨肿瘤坏死因子-α(TNF-α)在实验性小鼠慢性结肠炎发病过程中的作用。方法1999-04~2002-05比利时鲁汶大学医学院和郑州大学第一附属医院使用严重联合免疫缺陷型(SCID)小鼠,并体内移植入同基因源性CD45RB CD4+T细胞诱发慢性结肠炎发生。此结肠炎小鼠接受抗TNF-α单抗治疗,观察其疗效并研究其作用机制。结果当CD45RBhigh、CD4+T细胞植入SCID小鼠4周后,结肠黏膜有大量炎性细胞浸润,TNF-mRNA水平明显升高。抗TNF-单克隆抗体治疗有效地阻断慢性结肠炎发生,降低结肠黏膜内CD4+T细胞和单核巨噬细胞浸润,并显著地降低肠黏膜固有层CD4+T细胞白细胞介素-2(IL-2)和干扰素(INF)分泌。结论TNF-α参与慢性结肠炎的病理生理过程。阻断TNF-α体内分泌和效应应答可用于慢性结肠炎的临床治疗。
Objective To investigate the role of tumor necrosis factor-α (TNF-α) in the pathogenesis of experimental chronic colitis in mice. METHODS: From 1999-04 to 2002-05, severe combined immunodeficiency (SCID) mice were used in the School of Medicine of the University of Leuven in Belgium and the First Affiliated Hospital of Zhengzhou University. Chronic colitis was induced by transplantation of syngeneic CD45RB CD4 + T cells in vivo occur. The colitis mice received anti-TNF-α monoclonal antibody treatment to observe its efficacy and to study its mechanism of action. Results When CD45RBhigh and CD4 + T cells were implanted into SCID mice for 4 weeks, there was a large number of inflammatory cell infiltration in colonic mucosa and the level of TNF-mRNA was significantly increased. Anti-TNF monoclonal antibody treatment can effectively block the occurrence of chronic colitis, reduce the infiltration of CD4 + T cells and monocytes in the colonic mucosa and significantly reduce the CD4 + T cell interleukin-2 IL-2) and interferon (INF) secretion. Conclusion TNF-α is involved in the pathophysiology of chronic colitis. Blocking TNF-α in vivo secretion and response may be used for the clinical treatment of chronic colitis.