基于补体C5a在炎症性肠病中的作用研究  

Effect of complement C5a in inflammatory bowel disease

作　　者：周亚妮[1] 雷献文 宋云 ZHOU Ya-ni;LEI Xian-wen;SONG Yun(Shangluo Vocational and Technical College,Shangluo 726000,Shaanxi,China;Air Force Medical University,Xi’an 710032,Shaanxi,China)

机构地区：[1]商洛职业技术学院,陕西商洛726000 [2]空军军医大学,陕西西安710032

出　　处：《生物医学工程与临床》2020年第2期131-135,共5页Biomedical Engineering and Clinical Medicine

基　　金：陕西省教育厅专项科研计划项目(15JK1221);陕西省高等教育教学改革研究项目(19ZY022)。

摘　　要：目的探索2,4,6-三硝基苯磺酸(TNBS)诱导炎症性肠病(IBD)发病机制中补体C5a的作用。方法选择SPF级雄性Sprague-Dawley(SD)大鼠60只,鼠龄6~8周,体质量180~220 g。随机分为3组,即空白对照组、TNBS IBD组、TNBS+抗C5a单克隆抗体干预组(简称治疗组)。IBD大鼠建模方法采用TNBS联合乙醇诱导灌肠法。治疗组在建模后立即每只腹腔注射抗C5a单克隆抗体1.5 mg干预。利用酶联免疫吸附分析(ELISA)法检测不同时间段大鼠血清中炎性介质C5a和白细胞介素(IL)-6、肿瘤坏死因子α(TNF-α)的表达水平;另给予C5a拮抗剂后,再次检测大鼠血清中IL-6、TNF-α的表达水平。结果C5a、IL-6、TNF-α伴随着炎症的进展而增高,伴随炎症的转归出现下降趋势,即血清中C5a、IL-6、TNF-α的变化趋势与炎症反应程度呈正向相关性;给予C5a拮抗剂后,TNBS IBD组与治疗组相比,IL-6、TNF-α的表达水平有明显下调趋势,差异有统计学意义(P<0.05)。结论初步判断抗C5a单克隆抗体可能通过抑制IL-6、TNF-α的表达,有效地降低了IBD炎症反应,提示C5a在IBD发病机制中发挥着重要作用。Objective To study the effect of complement C5 a in the pathogenesis of inflammatory bowel disease(IBD)induced by2,4,6-trinitrobenzene sulfonic acid(TNBS).Methods Sixty male Sprague-Dawley(SD)rats of SPF grade were selected,aged6-8 weeks with body mass of 180-220 g,which were randomly divided into 3 groups:blank control group,TNBS IBD group,and TNBS+anti-C5 a monoclonal antibody intervention group(antibody intervention group).The IBD rats model was established by TNBS combined with ethanol-induced enema.The antibody intervention group was intraperitoneally injected with anti-C5 a monoclonal antibody 1.5 mg immediately after modeling.The expression levels of inflammatory mediator C5 a and cytokines interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in serum of rats at different time points were detected by enzyme linked immunosorbent assay(ELISA).The expression of IL-6 and TNF-αin serum was re-detected after C5 a antagonist.Results The C5 a,IL-6 and TNF-αincreased with inflammation progression,and decreased with inflammatory outcome.The changes of serum C5 a,IL-6 and TNF-αwere positively correlated with inflammatory reaction degree.After administration of C5 a antagonist,the expression levels of IL-6 and TNF-αin TNBS IBD group were significantly down-regulated than those in antibody intervention group,and the difference was statistically significant(P<0.05).Conclusion It is demonstrated that C5 a monoclonal antibody may effectively reduce inflammatory response of IBD by inhibiting expression of IL-6 and TNF-α,and C5 a plays an important role in pathogenesis of IBD.

关 键 词：抗C5a单克隆抗体 2 4 6-三硝基苯磺酸(TNBS) 炎症性肠病 白细胞介素6(IL-6) 肿瘤坏死因子α(TNF-α) 

分 类 号：R574.5[医药卫生—消化系统]