全反式维甲酸治疗葡聚糖硫酸钠诱导的小鼠结肠炎  

All-trans retinoic acid protects against dextran sulfate sodium-induced colitis in mice

作　　者：洪凯[1] 张翼[1] 郭媛[1] 白爱平[1] 

机构地区：[1]南昌大学第一附属医院消化内科,江西省南昌市330006

出　　处：《世界华人消化杂志》2013年第28期2902-2907,共6页World Chinese Journal of Digestology

基　　金：国家自然科学基金资助项目;Nos.81070310;81270472~~

摘　　要：目的:探讨全反式维甲酸(all-trans retinoic acid,ATRA)对葡聚糖硫酸钠(dextran sulfate sodium,DSS)结肠炎治疗作用的机制.方法:将小鼠随机分成4组:正常对照组、DSS组、DSS+ATRA组和DSS+LE135组.建立小鼠DSS结肠炎的急性模型,从小鼠饮用DSS第3天开始,DSS+ATRA组、DSS+LE135组分别给予ATRA 0.5 mg/d、LE135 0.1 mg/d腹腔注射至实验结束.每天观察各组小鼠疾病活动指数(disease activity index,DAI),第8天颈椎脱臼处死小鼠取肠组织匀浆检测各组小鼠炎症肠段中髓过氧化物酶(myeloperoxidase,MPO)的含量,ELISA检测肿瘤坏死因子-(tumor necrosis factor-,TNF-)的含量,免疫组织化学测定小鼠结肠CD68和核因子B(nuclear factor B,NF-B)P65的表达.结果:(1)DAI评分:DSS+ATRA组小鼠的DAI评分为4.63±2.20,与DSS组、DSS+LE135组相比评分明显较低(P<0.05);对照组小鼠的DAI评分均为0;(2)组织学评分:DSS+ATRA组小鼠的组织学评分为7.63±1.19,与DSS组(10.13±1.36)、DSS+LE135组(10.38±1.30)相比得分明显降低(P<0.05),但明显高于正常对照组(0.25±0.463);(3)MPO活性:DSS+ATRA组小鼠的MPO活性为7.88±0.68,与空白对照(3.52±0.58)、DSS组(11.36±0.96)、DSS+LE135组(12.65±0.77)相比均有明显差异(P<0.05);(4)组织匀浆TNF含量:DSS+ATRA组(178.63±39.37),明显低于DSS组(316.67±43.68)、DSS+LE135组(362.45±62.75)这2组;(5)结肠组织CD68的表达:DSS+ATRA组肠黏膜固有层CD68阳性细胞数明显低于DSS组、DSS+LE135组(P<0.05),与对照组小鼠的CD68表达量相比明显增高(P<0.05);(6)结肠组织NF-B的表达:DSS+ATRA组肠黏膜固有层NF-B阳性细胞数明显低于DSS组、DSS+LE135组(P<0.05),与对照组NF-B的表达量相比增高(P<0.05).结论:ATRA对DSS诱导的小鼠结肠炎具有治疗作用,机制为抑制结肠炎作用肠道免疫反应,及外周巨噬细胞向肠黏膜浸润.AIM： To investigate the effect of all-trans retinoic acid（ATRA）on dextran sulfate sodium（DSS）-induced colitis in mice.METHODS： Mice were randomly divided into four groups： a normal control group,a DSS group,an ATRA group,and a LE135 group.Except the normal control group,the other groups were fed 3%DSS（w/v）solution from days 1 to8 to induce colitis.The DSS group and ATRA group were intraperitoneally injected with ATRA 0.5 mg/d and LE135 0.1 mg/d from day3,respectively.Disease activity index（DAI）was recorded daily.The expression of CD68,NF- B p65,MPO activity,and TNF level in the colon of mice of each group were measured.RESULTS： DAI was significantly lower in theATRA group than in the DSS and LE135 groups（both P 0.05）.The histological score and MPO activity in colonic tissue in the ATRA group were significantly lower than those in the DSS and LE135 groups（histological score： 7.63 ± 1.19 vs10.13 ± 1.36,10.38 ± 1.30,both P 0.05; MPO activity： 7.88 ± 0.68 vs 11.36 ± 0.96,12.65 ± 0.77,both P 0.05）,but were higher than those in the control group（7.63 ± 1.19 vs 0.25 ± 0.463,P 0.05; 7.88 ± 0.68vs 3.52 ± 0.58,P 0.05）.The levels of TNF in colonic tissue were significantly lower in the ATRA group than in the DSS and LE135 groups（178.63 ±39.37 vs 316.67 ± 43.68,362.45 ± 62.75,both P 0.05）.The numbers of CD68 positive cells and NF- B positive cells in lamina propria in the ATRA group were significantly lower than those in the DSS and LE135 groups（all P 0.05）,but higher than those in the control group（all P 0.05）.CONCLUSION： ATRA protects against DSSinduced colitis in mice possibly by inhibiting immune cell activation in the lamina propria and infiltration of macrophage into colon tissue.

关 键 词：维甲酸 炎症性肠病 巨噬细胞 CD68 

分 类 号：R574.62[医药卫生—消化系统]