姜黄素联合MSCs对大鼠溃疡性结肠炎的影响及机制  

Therapeutic effects of curcumin combined with MSCs against ulcerative colitis in rats

作　　者：易金霞 费素娟[2] 庞迅雷[2] 吴克俭[2] 

机构地区：[1]徐州医学院,江苏省徐州市221002 [2]徐州医学院附属医院消化内科,江苏省徐州市221002

出　　处：《世界华人消化杂志》2014年第12期1642-1650,共9页World Chinese Journal of Digestology

摘　　要：目的:观察姜黄素联合骨髓间充质干细胞(marrow mesenchymal stem cell,MSCs)对大鼠溃疡性结肠炎(ulcerative colitis,UC)的疗效,并探讨辅助性T细胞17(T help cell 17,Th17)及调节性T细胞(regulatory T cell,Treg)平衡在其中的作用机制.方法:采用三硝基苯磺酸(trinitro-benzenesulfonic acid,TNBS)灌肠制备大鼠UC模型,将动物分为5组,分别为正常对照组(A组)、模型组(B组),MSCs组(C组),姜黄素组(D组),姜黄素联合MSCs组(E组).观察各组大鼠的行为、粪便性状及血便情况,计算结肠大体形态评分(gross morphological score,GMS)及病理损伤评分(histopathologic damage score,HDS),并通过流式细胞术(flow cytometer,FCM)检测各组Th17及Treg占CD4+T细胞的数量百分比;免疫组织化学(immunohistochemistry,IHC)检测白介素-17、Foxp3在结肠组织的表达.结果:(1)与正常组比较,模型组大鼠GMS、HDS均明显升高(0.00±0.00 vs 4.63±0.74;0.25±0.46 vs 4.00±0.53,P<0.01),Treg细胞在外周血及结肠组织的表达均下调,Th17的表达均上调,差异均有统计学意义(8.01±0.29 vs1.16±0.18;9.50±1.60 vs 0.88±0.64;0.63±0.13 vs 4.56±0.21;0.88±0.64 vs 7.75±1.16,P<0.01);(2)与模型组相比,各治疗组GMS、HDS均明显降低,差异有统计学意义(4.63±0.74 vs 2.12±0.64,2.00±0.53,1.00±0.53;4.00±0.53 vs 2.00±0.53,1.88±0.83,1.25±0.46,P<0.01);各治疗组Treg细胞表达均明显上调,而Th17细胞的表达均明显下调,差异有统计学意义(1.16±0.18 vs 3.29±0.18,3.19±0.20,5.00±0.19;0.88±0.64 vs 3.75±0.46,4.00±0.92,6.88±1.25;4.56±0.21 vs 2.60±0.15,2.59±0.23,1.52±0.21;0.88±0.64 vs3.75±0.46,4.00±0.92,6.88±1.25,P<0.01);(3)联合治疗组GMS、HDS较单药物治疗组降低(1.00±0.53 vs 2.12±0.64,2.00±0.53;1.25±0.46 vs 2.00±0.53,1.88±0.83,P<0.05),且Treg细胞表达均显著上调,而Th17细胞表达均显著下调,差异有统计学意义(5.00±0.19vs 3.29±0.18,3.19±0.20;6.88±1.25 vs 3.75±0.46,4.00±0.92;1.52±0.21 vs 2.60±0.15,2.59±0.23;2.38±0.92 vs 5.00AIM： To assess the therapeutic effects of curcumin combined with mesenchymal stem cells （MSCs） in the treatment of ulcerative colitis in rats and to explore the underlying mechanisms. METHODS： Ulcerative colitis was induced in rats with 2,4,6-trinitrobenzene sulfonic acid （TNBS）. 40 male Sprague-Dawley rats were randomly divided into 5 groups： a normal group, a model group, an MSCs group, a curcumin group, and a curcumin plus MSCs group. The signs and symptoms of rats in each group were observed, including vitality, diet, property of stool and bloody stool. The severity of colitis was assessed using gross morphological score （GMS） and histopathologic damage score （HDS）. The percentages of Th17 and Treg lymphocytesin peripheral blood were determined by flow cytometry. Expression of IL-17 and Foxp3 in the colonic mucosa was detected by immunohistochemistry. RESULTS： Compared with the normal group, the GMS and HDS were significantly higher in the model group （0.00 ± 0.00 vs 4.63 ± 0.74; 0.25 ± 0.46 vs 4.00 ± 0.53, P 〈 0.01）; the levels of Treg in the peripheral blood and Foxp3 in the colon tissue were significant decreased, and the levels of Th17 in the peripheral blood and IL-17 in the colon tissue were significantly increased in the model group （8.01 ± 0.29 vs 1.16 ± 0.18; 9.50 ± 1.60 vs 0.88 ± 0.64; 0.63 ± 0.13 vs 4.56 ± 0.21; 0.88 ± 0.64 vs 7.75 ± 1.16, P 〈 0.01 for all）. The GMS and HDS were significantly lower in the treatment groups than in the model group （4.63 ± 0.74 vs 2.12 ± 0.64, 2.00 _± 0.53, 1.00 ± 0.53; 4.00 ± 0.53 vs 2.00 ± 0.53, 1.88 ± 0.83, 1.25 ± 0.46, P 〈 0.01 for all）. The levels of Treg and Foxp3 were significantly increased, and the levels of Th17 and IL-17 were significantly decreased in the treatment groups compared with the model group （1.16 ~0.18 vs 3.29 ± 0.18, 3.19 ± 0.20, 5.00 ± 0.19; 0.88 ± 0.64 vs 3.75 ± 0.46, 4.00 ± 0.92, 6.88 ± 1.25; 4.56 ± 0.21 vs 2.60 ± 0.15, 2.59 ± 0.23, 1.52 ± 0.21; 0.88 ± 0.64 vs 3.75 �

关 键 词：溃疡性结肠炎 姜黄素 骨髓间充质干细胞 辅助性17细胞 调节性T细胞 

分 类 号：R574.62[医药卫生—消化系统]