核因子-κB小干扰RNA对葡聚糖硫酸钠诱导的小鼠结肠炎模型的影响

[Effects of nuclear factor-kappaB siRNA upon dextran sulphate sodium-induced colitis murine model].

作者信息

Cheng Li-na, Huang Xiao-li, Gan Hua-tian

机构信息

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Zhonghua Yi Xue Za Zhi. 2009 Sep 15;89(34):2416-9.

PMID:20137697

Abstract

OBJECTIVE

To investigate the effects of nuclear factor-kappaB (NF-kappaB) siRNA upon dextran sulphate sodium (DSS)-induced colitis.

METHODS

Thirty-six BALB/C mice were randomly divided into 4 groups: normal control group, NF-kappaB 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-alpha) level of colonic mucosa was measured by enzyme linked immunosorbent assay (ELISA). NF-kappaB 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-kappaB p65 siRNA (both P < 0.05). The expression of NF-kappaB p65 and TNF-alpha [(266 +/- 35) pg/ml] in mice with DSS-induced colitis was significantly reduced after treatment with NF-kappaB 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-kappaB p65siRNA shows protective effects upon the mice with DSS-induced colitis. Blockade of NF-kappaB pathway by NF-kappaB p65 siRNA may serve as a novel gene therapy for ulcerative colitis.

摘要

目的

探讨核因子-κB（NF-κB）小干扰RNA（siRNA）对葡聚糖硫酸钠（DSS）诱导的结肠炎的影响。

方法

将36只BALB/C小鼠随机分为4组：正常对照组、NF-κB siRNA组、乱序siRNA组和DSS组。通过在饮水中给予5% DSS诱导结肠炎，并通过疾病活动指数（DAI）和组织学评分进行评估。采用酶联免疫吸附测定（ELISA）法检测结肠黏膜肿瘤坏死因子（TNF-α）水平。通过免疫组织化学染色测定NF-κB p65表达。

结果

与乱序siRNA组（DAI 3.42±0.67，组织学评分4.65±1.53）和DSS组（3.73±0.55，4.47±1.52）相比，NF-κB p�5 siRNA小鼠的DAI（2.31±0.26）和组织学评分（2.19±0.77）显著降低（均P<0.05）。与乱序siRNA组[（412±51）pg/ml]和DSS组[（449±44）pg/ml]相比，用NF-κB p65 siRNA治疗后，DSS诱导的结肠炎小鼠中NF-κB p65和TNF-α的表达[（266±35）pg/ml]显著降低（P<0.05）。