脐带源间充质干细胞移植对慢性结肠炎小鼠环氧化酶2表达的影响  

Effect of human umbilical cord mesenchymal stem cells on cycloxygenase-2 expression in dextran sodium sulfate-induced chronic colitis

作　　者：刘蕾[1] 张红[1] 牛国超[1] 吴慧[1] 李辉[1] 张晓岚[1] 

机构地区：[1]河北医科大学第二医院消化科河北省消化病重点实验室河北省消化病研究所,河北石家庄050000

出　　处：《临床荟萃》2013年第7期763-768,F0003,共7页Clinical Focus

摘　　要：目的探讨人脐带源间充质干细胞(human umbilical cord mesenchymal stem cells,hUC-MSCs)移植对慢性实验性结肠炎小鼠肠黏膜炎症的治疗作用及其机制。方法 55只C57BL/6小鼠随机分为正常对照组、右旋葡聚糖硫酸钠(dextran sodium sulfate,DSS)+vehicle组(溶剂对照组)和DSS+hUC-MSCs组,其中正常对照组15只,其余两组各20只。通过饮用2%DSS建立慢性实验性结肠炎模型,DSS+hUC-MSCs组在造模第14天时经尾静脉注射1×106/200μl的hUC-MSCs,正常对照组与DSS+Vehicle组则给予等体积磷酸盐缓冲液(Phosphate BufferedSaline,PBS)作为对照,分别于hUC-MSCs移植后1、2和4周处死动物。结肠黏膜炎症改变的评估包括每天体质量改变、疾病活动指数(disease activity index,DAI)、结肠长度等指标,以及结肠形态学改变和组织病理学评分,同时应用免疫组织化学方法检测结肠组织中环氧化酶2(cyclooxygenase-2,COX-2)的表达。结果与正常对照组比较,DSS+Vehicle组小鼠DAI、结肠形态学评分及结肠组织病理评分均显著增加(P<0.01),经过hUC-MSCs移植各项指标均显著降低(P<0.01);免疫组织化学染色显示DSS+Vehicle组较正常对照组小鼠结肠组织COX-2蛋白表达明显增加(移植1周0.387±0.013vs 0.065±0.015,移植2周0.548±0.037vs 0.065±0.015,移植4周0.606±0.034vs0.065±0.015,P<0.01),经过hUC-MSCs移植,结肠组织COX-2蛋白表达较DSS+Vehicle组明显降低(移植2周0.446±0.030vs 0.548±0.037,移植4周0.331±0.026vs 0.606±0.034,P<0.01)。结论 hUC-MSCs移植可减轻慢性结肠炎肠黏膜炎症,其机制可能与抑制结肠组织炎症因子COX-2表达有关。Objective To intvestigate the protective role of human umbilical cord mesenchymal stem cells（hUC- MSCs） in colonic mucosal inflammation in chronic experimental colitis and its possible mechanism. Methods Chronic colitis was induced by administration of dextran sodium sulfate（DSS） in drinking water. A total of 55 mice were randomly divided into normal control （ n = 15）, DSS＋ vehicle（ n= 20） and DSS＋ hUC-MSCs group （ n = 20）. The mice in the DSS＋ hUC-MSCs group received 1× 10^6/200 μ1 hUC-MSCs via the tail vein on day 14 and the mice in control and DSS＋vehicle group were given normal phosphate buffer saline（PBS） for comparison. Mice were killed on weeks 1,2 and 4 after hUC-MSCs injection. The severity of colitis was evaluated by body mass（BM） changes, disease activity index（DAD, colon length, colon histology changes and pathology score. The expression of cycloxygenase-2 （COX-2） in the colon tissue was detected by immunohistochemistry. Results The results of severity of chronic colitis showed that DAI （ P〈0.01） and pathology scores （ P〈0.01） in DSS＋ vehicle group were significantly higher than those of the control group,the colon length was shorter （ P〈0.01） ,and also the degree of the congestion and edema of the colon wall and infiltration of granulocytes into the mucosa were much severer in DSS＋ vehicle group. While after the transplantation of hUC-MSCs,DAI （ P〈0.01） and pathology score （ P〈0, 01） evidently decreased in DSS＋ hUC-MSCs group, colon length was longer （ P〈0.01）,and the degree of the congestion and edema of the colon wall and infiltration of granulocytes into the mucosa were improved （ P〈0.01）. The results of immunohistochemical staining showed that the expression of the COX-2 protein in colon tissue significantly increased in the DSS＋vehicle group compared with that in control group （P〈0.01）. While after the transplantation of hUC-MSCs, COX-2expression significantly decreased in the DSS＋hUC-MSCs group

关 键 词：结肠炎 溃疡性 间充质干细胞移植 环氧化酶2 

分 类 号：R574.62[医药卫生—消化系统]