英夫利昔单抗对溃疡性结肠炎大鼠的疗效评价与作用机制研究  

Research on the therapeutic effects and mechanisms of Infliximab in ulcerative colitis model of rats

作　　者：崔梅花[1] 刘献民[1] 牟方宏[1] 杨友鹏 

机构地区：[1]航天中心医院(北京大学航天临床医学院)消化科,北京100049

出　　处：《中国现代医学杂志》2012年第2期15-19,共5页China Journal of Modern Medicine

基　　金：航天中心医院科研基金(No:200606)

摘　　要：目的评价英夫利昔单抗治疗溃疡性结肠炎(UC)实验大鼠的效果,并初步探讨其作用机制。方法40只健康雄性Wistar大鼠随机分成正常对照组、损伤组、泼尼松组和英夫利昔组,每组10只,其中后3组建立三硝基苯磺酸(TNBS)UC大鼠模型。英夫利昔组给予英夫利昔30 mg/kg腹腔注射,造模第7天、14天各给药1次;泼尼松组给予泼尼松6 mg/kg灌胃,正常对照组和损伤组给予等体积生理盐水灌胃,造模第7～20天每日1次灌胃;造模第21天处死大鼠。观察各组大鼠结肠黏膜的病理改变,并用酶联免疫法(ELISA)检测各组大鼠的外周血清、结肠黏膜及脾脏中肿瘤坏死因子α(TNF-α)、白介素-10(IL-10)的含量。结果病理组织学观察显示,正常对照组结肠黏膜结构基本正常,损伤组可见典型黏膜炎症表现,泼尼松组和英夫利昔组炎症病变明显减轻。TNF-α、IL-10检测显示,与正常对照组比较,损伤组外周血清、结肠黏膜、脾脏中的TNF-α含量升高、IL-10含量降低(P<0.05);与损伤组比较,英夫利昔组外周血清、结肠黏膜、脾脏中的TNF-α降低,外周血清、结肠黏膜的IL-10含量升高(P<0.05),其中英夫利昔组血清及肠黏膜的TNF-α含量较泼尼松组降低(P<0.05);各组脾脏组织中IL-10含量的差异无统计学意义(P>0.05)。结论英夫利昔单抗能改善UC大鼠结肠黏膜的炎症病理改变,对UC大鼠有较好的治疗效果;其作用是通过抑制体内TNF-α的表达及提高IL-10的表达而实现的。[ Objectives] To study the effects of Infliximab in ulcerative colitis （UC） model of rats, and to explore the potential pathogenesis. [Methods ] Forty healthy male Wistar rats were divided randomly into normal control group, damaged group, prednisone group and Infliximab group, with each group of ten, and the latter three groups were established models of UC by enema with trinitrobenzene sulfonie acid （TNBS）. Infliximab group was treated by intraperitoneal injection of Infliximab with dose of 30 mg/kg on days 7 and 14 after modeling respectively. Prednisone group got treated by gastric perfusion of prednisone with dose of 6 mg/kg on days 7 to 20 everyday, also normal control group and damaged group were addressed by equal physiological saline in the same way. We detected the levels of tumor necrosis factor-alpha （TNF-α and interleukin- 10 （IL-IO） in peripheral blood, colonic mucosa and spleen by ELISA after the rats were all put to death on days 21. [Results] Histopathological observation found that colonic mucosa of normal control group was normal, that of damaged group was typical inflammatory injury, and inflammatory lesion of prednisone group or the Infliximab group was significantly reduced. Compared with normal control group, TNF-α of damaged group in peripheral blood, colon, spleen tissue was significantly higher, IL-10 was significantly lower （P〈0.05）.Compared with damaged group, TNF-α of the Infliximab group was decreased significantly, while IL-10 increased significantly （P 〈0.05）. TNF-ct levels in serum and intestinal mucosa of the Infliximab group were lower than those of the prednisone group （P 〈0.05）. However, there was no significant difference of the IL- l0 levels of the spleen between different groups （P〉0.05）. [Conclusion] The data obtained revealed that Infliximab can improve the pathological inflammation of UC colon mucosa, and that inhibiting the expression of TNF-α and enhancing the expression of IL-10 in vivo maybe contribute to the therapeutic effe

关 键 词：英夫利昔单抗 肿瘤坏死因子α(TNF—α) 白介素-10(IL-10) 溃疡性结肠炎 

分 类 号：R-332[医药卫生] R574.62