IL-27在小鼠结肠炎中的作用及对NLRP3炎性小体的影响  

Role of IL-27 in mouse colitis model and its influence on NLRP3 inflammasome

作　　者：张目涵 周力为 贺欣[1] 路瑶[1] 赵美华[1] 马娜[1] 冯百岁[1] ZHANG Mu-han;ZHOU Li-wei;HE Xin;LU Yao;ZHAO Mei-hua;MA Na;FENG Bai-sui(Department of Gastroenterology,The Second Affiliated Hospital of Zhengzhou University,Inflammatory Bowel Disease Center,Wu Jie ping Medical Fourudation,China Inflammatory Bowel Disease Coalition,Henan Inflammatory Bowel Disease Center,Zhengzhou 450014,China)

机构地区：[1]郑州大学第二附属医院消化内科,炎症性肠病中心,吴阶平医学基金会中国炎症性肠病联盟河南省炎症性肠病中心,河南郑州450014

出　　处：《中国病理生理杂志》2018年第6期1089-1094,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81070288;No.81270452); 河南省卫生计生科技创新型人才特聘学科带头人; 河南省自然科学基金资助项目(No.162300410268); 河南省医学科技攻关计划项目(No.201502015)

摘　　要：目的:观察白细胞介素27(IL-27)对葡聚糖硫酸钠(DSS)诱导的结肠炎小鼠结肠组织学及NOD样受体蛋白3(NLRP3)炎性小体的影响。方法:将48只雄性C57BL/6小鼠随机分为正常对照组(自由进食饮水)、DSS模型组(饮用3%DSS溶液)、低剂量IL-27组和高剂量IL-27组(在饮用DSS溶液的基础上分别腹腔注射500ng和1μg IL-27)。12 d后行疾病活动指数(DAI)及组织损伤指数(HI)评分评估炎症程度,取结肠组织行免疫组化、Western blot及qPCR检测,取血清行ELISA检测IL-1β和IL-18水平。结果:与对照组相比,模型组的DAI评分和HI评分提示小鼠的结肠炎症明显增强(P<0.05),NLRP3和IL-1β的mRNA表达水平增高,NLRP3和cleaved caspase-1的蛋白水平增高,血清中IL-1β和IL-18的含量增加;与模型组相比,高剂量IL-27组的DAI评分和HI评分提示小鼠的结肠炎症明显减轻(P<0.05),NLRP3和IL-1β的mRNA表达水平下降,NLRP3和cleaved caspase-1的蛋白水平降低,血清中IL-1β中和IL-18的含量也减少;与模型组比较,低剂量IL-27组除了血清中IL-1β和IL-18含量减少外,上述各项指标的差异无统计学显著性。结论:IL-27可减轻DSS结肠炎模型小鼠的炎症程度并且可抑制NLRP3炎性小体的表达和激活。AIM： To observe the effect of interleukin-27（ IL-27） on the pathological changes and the expression and activation of NOD-like receptor protein 3（ NLRP3） inflammasome in the colonic tissues of the mice with dextran sodium sulfate（ DSS）-induced experimental colitis. METHODS： Male C57 BL/6 mice（ n = 48） were randomly divided into control group（ given unrestricted diet）,DSS group（ drinking 3% DSS solution）,IL-27（ 500 ng） group and IL-27（ 1μg） group（ intraperitoneal injection of 500 ng and 1 μg IL-27 on the basis of drinking DSS solution,respectively）. After treatment for 12 d,intestinal inflammation in the mice was evaluated,the pathological changes of the colonic tissues were observed by HE staining,and the disease activity index（ DAI） score and histological index（ HI） score were calculated.The colonic tissues were collected for immunohistochemistry,qPCR and Western blot detections. The serum was prepared for ELISA. RESULTS： Compared with control group,the DAI score and HI score in model group indicated that the colonic inflammation was more obvious（ P〈0. 05）,the mRNA expression of NLRP3 and IL-1β was increased,the protein levels of NLRP3 and cleaved caspase-1 were elevated,and the releases of IL-1β and IL-18 in the serum were also increased（ P〈0. 05）. Compared with DSS group,the DAI score and HI score in IL-27（ 1 μg） group indicated that the colonic inflammation was obviously attenuated,the mRNA expression of NLRP3 and IL-1β was decreased,the protein levels of NLRP3 and cleaved caspase-1 were suppressed,and the releases of IL-1β 和 IL-18 in the serum were also decreased（ P〈0. 05）. No difference of the above indexes between DSS group and IL-27（ 500 ng） group was observed except the decreases in the releases of IL-1β and IL-18 in the serum in IL-27（ 500 ng） group. CONCLUSION： IL-27 alleviates the inflammation in DSS-induced colitis mice and inhibits the expression and activation of NLRP3 inflammasome.

关 键 词：白细胞介素27 NLRP3炎性小体 炎症性肠病 结肠炎 

分 类 号：R363[医药卫生—病理学] R547.6[医药卫生—基础医学]