构建表达IL-2的大肠埃希菌对小鼠肠炎的影响

The effects of Oral E.coli 1917 expressing IL-2 on experimental colitis in mice

目的以Escherichia coli Nissle 1917为基础建立一种与肠道菌群相关的新型白介素2(IL-2)递送方式,研究其对葡聚糖硫酸钠(DSS)诱导的实验性结肠炎的治疗作用。方法将小鼠随机分为4组(每组10只),以正常小鼠作为空白对照组,实验组小鼠用3%的DSS水诱导小鼠结肠炎模型,分别灌胃表达IL-2的菌株(E.coli 1917/IL-2)、空质粒转化的菌株(E.coli 1917/0)或PBS进行治疗5 d,定期评估各组小鼠的临床体征、疾病活动指数(DAI)、病理和免疫组织学变化。结果构建的益生工程菌E.coli 1917/IL-2可有效缓解DSS诱导的小鼠肠炎,小鼠DAI评分较低,体质量及结肠长度均高于对照组,肠黏膜组织中炎症细胞浸润较少。结论使用工程化益生大肠埃希菌编码免疫调节细胞因子的治疗策略为溃疡性结肠炎提供一种潜在的治疗方法。

Objective To establish a delivery system of Interleukin 2(IL-2)based on E.coli Nissle 1917 and explore its therapeutic effect on experimental colitis induced by dextran sulfate sodium(DSS).Methods Normal mice were used as blank controls and 3%DSS water was used to induce experimental colitis in experimental mice.The mice in the experiment group were randomly given oral E.coli 1917/IL-2,empty plasmid transformed E.coli 1917(E.coli 1917/0)or PBS for 5 days.The severity of colitis was periodically evaluated according to clinical signs,disease activity index(DAI)and pathological and immunohistological changes in different treatment groups.Results Oral E.coli 1917/IL-2 effectively improved the weight and colon length of colitis mice,and reduced the infiltration of inflammatory cells.Conclusion Therapeutic strategies using engineered E.coli-encoded immunomodulatory cytokines provide a potential treatment for ulcerative colitis.