抗肿瘤坏死因子-α抗体对慢性结肠炎小鼠肠黏膜组织内淋巴细胞凋亡的影响  

Effect of anti-TNF-α antibody on mucosal lymphocyte apoptosis in chronic colitis mice

作　　者：刘占举[1] 徐刚[1] 崔静[1] 唐芙爱[1] 

机构地区：[1]郑州大学第二附属医院消化内科,郑州450014

出　　处：《郑州大学学报（医学版）》2006年第5期821-822,共2页Journal of Zhengzhou University(Medical Sciences)

基　　金：*国家自然科学基金资助项目30571751;教育部"新世纪优秀人才支持计划"基金资助项目NCET-05-0609

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。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 rive administration of anti-TNF-α effectively prevents chronic colitis through the induction of intestinal mucosal lymphocyte apoptosis and the inhibition of mucosal lymphocyte function.

关 键 词：肿瘤坏死因子-α 结肠炎 单克隆抗体 凋亡 小鼠 

分 类 号：R574.62[医药卫生—消化系统]