【摘要】 目的:探讨抗肿瘤坏死因子(TNF)-α单抗在阻断小鼠慢性结肠炎发生过程中的作用机制。方法:严重联合免疫缺陷型(SCID)小鼠(n=24)体内植入同基因源性CD45RBhighCD4+T细胞,以诱导慢性结肠炎发生。SCID小鼠造模后均分为观察组和对照组,分别采用抗TNF-α单抗和大鼠免疫球蛋白治疗,剂量均为1mg/只,1次/周,腹腔注射,连续治疗8周。每周记录小鼠的体质量、大便情况和脱肛症状等。SCID小鼠均于造模8周后处死,采集升结肠组织进行组织病理学观察;采用TUNEL染色法检测肠黏膜内淋巴细胞凋亡情况。结果:对照组小鼠均表现为体质量下降,发生腹泻和脱肛,结肠壁增厚,结肠黏膜组织内有大量淋巴细胞浸润,有溃疡发生。观察组小鼠体质量增加,无腹泻和大便稀软现象,结肠黏膜组织结构完整,黏膜和黏膜下层仅有少量的淋巴细胞浸润。观察组小鼠结肠黏膜组织内每高倍视野TUNEL阳性细胞数(56.5±8.2)高于对照组(4.3±0.6)(t=4.521,P<0.001)。结论:抗TNF-α单抗可诱导结肠黏膜内淋巴细胞的凋亡,抑制淋巴细胞功能,从而阻断慢性结肠炎发生。更多还原

【Abstract】 Aim: To investigate the mechanisms of anti-TNF-α monoclonal antibody(mAb) in the prevention of murine chronic colitis in mice.Methods: A total of 24 severe combined immunodeficient (SCID) mice were injected syngenetic CD45RB high CD4+ T cells,and then equally allocated into two groups: Group A and group B. Mice in group A and B were intraperitoneally given anti-TNF-α mAb and Ig for 8 weeks, respectively. The weight, incidence of soft stool and diarrhea were recorded every week, and apoptosis of intestinal mucosal lymphocytes were assessed by TUNEL staining after the treatment.Results: Weight decrease, soft stool and diarrhea, and large lymphocyte infiltration in colonic mocosa of group B were observed, while increase of body weight, absence of diarrhea, and few lymphocyte infiltration in lamina propria of colonic mucosa occurred in group A. The number of TUNEL-positive lymphocytes in colonic mucosa of Group A were ( 56.5±8.2)/HP, higher than that of (4.3±0.6)/HP of Group B(t=4.521,P<0.001). Conclusion: In vivo administration of anti-TNF-α effectively prevents chronic colitis through the induction of intestinal mucosal lymphocyte apoptosis and the inhibition of mucosal lymphocyte function.更多还原