乌司他丁对溃疡性结肠炎大鼠结肠炎症及TLR4/NF-κB信号通路的影响  

Effect of Ulinastatin upon Inflammation and TLR4/NF-κB Signaling Pathway in Ulcerative Colitis Rats Model

作　　者：赵承满[1] 孟立娜[2] 陈锦龙[1] 陈方明[3] 

机构地区：[1]浙江萧山医院消化内科,杭州311200 [2]浙江中医药大学附属第一医院消化内科,杭州310006 [3]浙江中医药大学动物实验研究中心,杭州310053

出　　处：《中国现代应用药学》2017年第3期347-351,共5页Chinese Journal of Modern Applied Pharmacy

基　　金：杭州市科委重点专科专病科研攻关基金项目(20140633B53)

摘　　要：目的观察乌司他丁对溃疡性结肠炎的作用,以及对Toll样受体4(TLR4)/核因子-κB(NF-κB)信号通路的干预作用,以探讨其可能的作用机制。方法采用三硝基苯磺酸灌肠法制备溃疡性结肠炎大鼠模型。SD大鼠80只随机分成空白组、模型组、乌司他丁组(乌司他丁50 000 U·kg-1·d-1腹腔注射)、激素组(泼尼松片6 mg·kg-1·d-1灌胃给药),每组20只。造模7 d后处死,检测各组大鼠结肠黏膜大体评分(CMDI评分)和病理组织学评分变化;ELISA法检测各组大鼠血清TNF-α水平;免疫组化法观察大鼠结肠组织TLR4及NF-κB蛋白的表达。结果模型组大鼠结肠大体形态损伤及病理组织学评分均高于空白组(P均<0.01),大鼠造模成功;与模型组比较,乌司他丁组CMDI评分及病理组织学评分均减低(P均<0.05),与激素组比较,乌司他丁组CMDI评分及病理组织学评分则无差异。模型组大鼠的血清TNF-α与空白组比较,水平明显上升(P<0.01);而乌司他丁组与模型组比较,大鼠血清TNF-α水平则明显下降(P<0.05),乌司他丁组与激素组比较则无明显差别。与空白组比较,模型组大鼠肠黏膜中TLR4、NF-κB均呈明显高表达(P<0.01),乌司他丁组TLR4、NF-κB表达较模型组则明显下降(P均<0.05),而乌司他丁组中NF-κB的表达则又低于激素组(P<0.05),TLR4的表达则与激素组无明显差异。结论乌司他丁能减轻溃疡性结肠炎大鼠肠道炎症反应,具有治疗作用;其机制可能与通过下调TLR4及NF-κB的表达,减少炎症因子TNF-α的释放有关。OBJECTIVE To observe the effect of ulinastatin on ulcerative colitis（UC）, and its intervention effect on toll-like receptor 4（TLR4）/NF-kappa B（NF-κB） signaling pathway, thus to investigate its possible mechanism. METHODS Trinitrobenzene sulfonic acid（TNBS）/ethanol enema method was used to set up the UC rat model. Eighty male Wistar rats were randomly divided into blank group; model group, ulinastatin group（received ulinastatin 50 000 U·kg^-1·d^-1 by intraperitoneal injections）, corticosteriod group（prednisone tablets 6 mg·kg-1·d-1 intragastric administration）, with 20 rates in each group. All the rats were sacrificed one week after modeling, the gross score of colonic mucosa（CMDI score） and histological grading of each group were observed. The serum levels of TNF-α were determined by ELISA. Expression of TLR4 and NF-κB in colon mucosa were further detected by immuno-histochemistry. RESULTS The colon gross morphological damage, and the histological score of the model group rats were significantly higher than those of the blank group（all P〈0.01）, indicated successful establishment of UC model. Compared with the model group, the CMDI score and pathological score in ulinastatin group were decreased（all P〈0.05）. There were no differences of the CMDI score and pathological score between the corticosteriod group and ulinastatin group. The levels of serum TNF-α in model group rats were significantly higher than those of the blank group rats（P〈0.01）. Compared with the model group, the serum levels of TNF-α in ulinastatin group were significantly decreased（P〈0.05）, which were no significant differences between the corticosteriod group and the ulinastatin group. Compared with the blank group, the expression of NF-κB and TLR4 in model group significantly enhanced（P〈0.01）, which in ulinastatin group were lower than the model group（all P〈0.05）. The expression of NF-κB in ulinastatin group was lower than the corticosteriod group（P〈0.05）, and the ex

关 键 词：乌司他丁 溃疡性 结肠炎 TOLL样受体 NF-ΚB 

分 类 号：R965.2[医药卫生—药理学]