核因子κB小干扰RNA对葡聚糖硫酸钠诱导小鼠结肠炎的影响  

Effects of nuclear factor-κB siRNA upon dextran sulphate sodium-induced colitis murine model

作　　者：程黎娜[1] 黄晓丽[2] 甘华田[2] 

机构地区：[1]四川大学华西医院消化内科,成都610041 [2]四川大学华西医院老年消化科,成都610041

出　　处：《中华医学杂志》2009年第34期2416-2419,共4页National Medical Journal of China

基　　金：国家自然科学基金（30770983）;四川省科技厅攻关课题基金（2006209-011）

摘　　要：目的探讨核因子κB小干扰RNA（siRNA）对葡聚糖硫酸钠（DSS）小鼠结肠炎的影响，为寻找治疗溃疡性结肠炎（UC）的新药提供实验依据。方法36只BALB／C小鼠随机分为4组（每组9只）：正常对照组、核因子κB siRNA组、错义siRNA组、DSS模型组。每日观察各组小鼠的体重、活动、大便性状和便血情况以评估小鼠的疾病活动情况；对小鼠结肠组织进行大体及组织形态学观察；免疫组织化学染色观察核因子κBp65在结肠黏膜内的表达；酶联免疫吸附法（ELISA）测定结肠黏膜组织中肿瘤坏死因子（TNF-α）的含量。结果（1）核因子KBsiRNA组小鼠的DAI评分[（2．31±0．26）分]和组织学评分[（2．19±0．77）分]明显低于错义siRNA组[（3．42±0．67）分和（4．65±1．53）分]及DSS模型组[（3．73±0．55）分和（4．47±1．52）分，均P〈0．05]。（2）核因子κBsiRNA组小鼠结肠黏膜核因子κBp65的阳性表达及结肠黏膜组织内TNF-α含量[（266±35）pg／m1]明显低于错义siRNA组[（412±51）pg／ml]和DSS模型组[（449±44）pg／ml，均P〈0．05]。结论核因子κBp65siRNA对小鼠DSS结肠炎有一定的治疗作用，核因子κBp65siRNA有望成为一种新型的治疗UC的基因药物。Objective To investigate the effects of nuclear factor-κB （NF-κB） siRNA upon dextran sulphate sodium （DSS） -induced colitis. Methods Thirty-six BABL/C mice were randomly divided into 4 groups： normal control group, NF-κB siRNA, scrambled siRNA and DSS group. Colitis was induced by treatment with 5% DSS in drinking water and evaluated by disease activity index （DAI） and histological score. The tumor necrosis factor （TNF-α） level of colonic mucosa was measured by enzyme linked immunosorbent assay （ELISA）. NF-κB p65 expression was determined by immunohistochemical staining. Results Compared with the scrambled siRNA （ DAI 3.42 ± 0. 67, histological score 4. 65 ±1. 53 ） and DSS group（3.73 ± 0. 55,4.47 ± 1.52 ）, a significant decrease was observed in DAI （ 2. 31 ± 0. 26 ） and histological score（2. 19 ± 0. 77）in mice with NF-κB p65 siRNA （both P 〈 0. 05）. The expression of NF-κB p65 and TNF-α [ （ 266± 35 ） pg/ml ] in mice with DSS-induced colitis was significantly reduced after treatment with NF-κB p65 siRNA （ P 〈 0. 05 ） in comparisons with the scrambled siRNA [ （ 412 ± 51 ） pg/ml ] and DSS group pg/ml[ （449±44） pg/ml]. Conclusion NF-κB p65siRNA shows protective effects upon the mice with DSS-induced colitis. Blockade of NF-κB pathway by NF-κB p65 siRNA may serve as a novel gene therapy for ulcerative colitis.

关 键 词：结肠炎 溃疡性 NF—κB RNA 小分子干扰 肿瘤坏死因子α 

分 类 号：R686[医药卫生—骨科学]