靶向抑制巨噬细胞Act1表达对溃疡性结肠炎的作用  

Targeted suppression of Act1 in the macrophages ameliorates experimental ulcerative colitis in mice induced by dextran sodium sulfate

作　　者：郐一贺 王丽京[1] 邓慧君[2] 陈佳园[2] 顾取良[1] KUAI Yi-he WANG Li-jing DENG Hui-jun CHEN Jia-yuan GU Qu-liang(Vascular Biology Research Institute, School of Basic Sciences School of Health Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China)

机构地区：[1]广东药科大学基础学院血管生物学研究所,广州510006 [2]广东药科大学健康学院,广州510006

出　　处：《中国实验动物学报》2016年第6期585-590,共6页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金项目(编号:31471290)

摘　　要：目的探讨巨噬细胞NF-κB活化因子1(nuclear factor kappa B activator 1,Act1)在炎症性肠病中的作用。方法以巨噬细胞Act1表达被靶向抑制的小鼠(anti-Act1)为研究对象,利用葡聚糖硫酸钠(dextran sodium sulfate,DSS)诱导溃疡性结肠炎模型,通过检测小鼠体重变化、便血情况、粪便黏稠度等进行疾病活动指数评分,对结直肠组织进行HE染色评价炎症严重程度,免疫组化方法分析白细胞和巨噬细胞等的浸润情况并用RT-q PCR法检测相关细胞因子的表达变化。结果在DSS诱导7 d后与C57小鼠相比,anti-Act1小鼠结直肠炎症指标评分较低,巨噬细胞等浸润数量较少,TNF-α、IL-1β和IL-6 mRNA表达较低。结论靶向抑制巨噬细胞Act1表达能够减轻DSS诱导的溃疡性结肠炎。Objective To investigate the role of macrophage-derived Act1（ nuclear factor kappa B activator 1） in the inflammatory bowel disease. Methods Genetically engineered mice carrying targeted suppression of Act1 in the macrophages（ Anti-Act1） were used for the dextran sodium sulfate（ DSS）-induced ulcerative colitis. The severity of colitis was assessed by weight loss,stool consistency,fecal blood index,colorectal length and HE histology. The infiltration of CD45＋leukocytes and CD68＋macrophages in the inflammatory intestine was observed by immunohistochemical staining and expression levels of mRNA for inflammatory cytokines in colon tissues were analyzed by RT-q PCR. Results As compared with C57 mice,the anti-Act1 mice exhibited less severe acute colitis following DSS treatment,with reduced CD45＋leukocyte and CD68＋macrophage infiltrates in the colon tissue. Inflamed colons of the anti-Act1 mice expressed lower mRNA levels of TNF-α,IL-1β and IL-6. Conclusions Targeted suppression of Act1 in the macrophages ameliorates dextran sodium sulfate-induced intestinal inflammation.

关 键 词：Act1 基因工程小鼠 溃疡性结肠炎 巨噬细胞 

分 类 号：Q95-33[生物学—动物学]