摘要
目的探讨抗巨噬细胞移动抑制因子单抗(抗MIF单抗)对小鼠急性溃疡性结肠炎(UC)发病的干预作用及其可能调控机制。方法以葡聚糖硫酸钠(DSS)诱导制备小鼠急性UC模型,小鼠分为正常组、UC模型组、抗MIF单抗干预组和生理盐水组。造模及药物干预期间观察小鼠一般情况并行疾病活动指数(DAI)评分,7 d后断颈处死全部小鼠,行结肠大体损伤评分,HE染色后光镜下观察结肠病理改变,免疫组化染色观察巨噬细胞移动抑制因子(MIF)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)等促炎因子在结肠组织炎症细胞的表达情况,实时荧光定量PCR(real-time PCR)检测结肠组织核因子-κβ(NF-κβ)p65 mRNA的表达水平。结果与正常组相比,其余三组小鼠结肠炎症病变明显,MIF、TNF-α、IL-6等促炎因子的表达水平明显升高(P<0.05);与模型组相比,干预组结肠黏膜损伤程度减轻,抗MIF单抗显著改善MIF、TNF-α、IL-6等促炎因子的表达水平(P<0.05),而生理盐水组与其差异无统计学意义(P>0.05)。real-time PCR结果显示应用抗MIF单抗的小鼠能显著抑制结肠组织NF-κβp65 mRNA的表达水平。结论抗MIF单抗对小鼠UC的发病有明显的干预作用,可能通过抑制NF-κβ信号通路,减少促炎因子的表达发挥作用。
Objective To investigate the protective effect and possible regulatory mechanism of anti-macrophage migration inhibitory factor monoclonal antibody （anti-MIF Ab）on acute ulcerative colitis （UC） in mice. Methods Acute ulcerative colitis model in mice was established by dextran sulfate sodium （DSS）, to observe the protective effect of anti-MIF Ab on ulcerative eolotis in mice. The experiment was divided into normal group, UC model group, anti-MIF Ab intervention group and saline group. During modeling and the period of administration, to ob- serve general situations and score Disease Activity Index （DAI） of mice, after 7 days, all mice were killed, per- forming the gross damage score in colon, observing the colonic histopathological changes under the light microscope on HE staining, viewing the expression conditions of serum inflammatory cytokins such as MIF,TNF-α, IL-6 in in- testinal inflammatory cells on immunohistochemieal staining, using real-time quantitative （real-time PCR） to ana- lyze the expression levels of NF-Kβ p65 mRNA in colon tissue. Results Compared with the normal group, the de- grees of colonic inflammation were significantly severe in the other three groups, the expression levels of serum in- flammatory cytokines such as MIF,TNF-α, IL-6 were remarkably increased （ P 〈 0. 05 ） ; compared with the model group, the degrees of colonic mucosa damage were alleviated in intervention group. Anti-MIF Ab could obviously improve the expression levels of serum inflammatory cytokines such as MIF, TNF-α, IL-6 （P 〈 0.05 ） , but no sig- nificant differences between saline group and model group. The results of real-time PCR showed that mice using an- ti-MIF Ab could apparently inhibit the expression level of NF-Kβ p65 mRNA. Conclusion Anti-MIF Ab has a strongly protective effect against ulcerative colitis in mice, maybe the inhibition of NF-Kβ signal pathway and the decreasion of inflammatory eytokines play a central factor resulting from this conclusion.
出处
《安徽医科大学学报》
CAS
北大核心
2016年第1期31-35,共5页
Acta Universitatis Medicinalis Anhui
基金
广西医疗卫生重点科研课题(编号:重2011018)
桂林市科学研究与技术开发计划项目(编号:科技攻关20140120-7-2)
关键词
抗巨噬细胞移动抑制因子单抗
葡聚糖硫酸钠
溃疡性结肠炎
炎症因子
核因子-κβ
anti-macrophage migration inhibitory factor monoclonal antibody
dextran sulfate sodium
ulcerative colitis
inflammatory factor
nuclear factor-Kβ
