Bortezomib对炎症性肠病小鼠模型炎症抑制作用及机制的研究  

The inhibitory effect and mechanism of Bortezomib on mice model with inflammatory bowel disease

作　　者：胡丽红[1] 李晴[1] 曲波[1] 张志荣 HU Lihong1, LI Qing1, Qu Bo1, ZHANG Zhirong2(1. Department of Gastroenterology, the Second Affiliated Hospital of Harbin Medical University, Harbin 150086 ; 2. 2014 Grade of Clinical Medicine, Harbin Medical University, Chin)

机构地区：[1]哈尔滨医科大学附属第二医院消化内科,黑龙江哈尔滨150086 [2]哈尔滨医科大学

出　　处：《胃肠病学和肝病学杂志》2018年第3期286-290,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：黑龙江省卫生计生委科研课题(2014-332)

摘　　要：目的观察Bortezomib能否通过抑制核因子-κB(nuclear factor-κB,NF-κB)活性起到治疗炎症性肠病(inflammatory bowel disease,IBD)的作用。方法 160只Balb/c小鼠随机分成Bortezomib高、中、低剂量治疗组,正常对照组和模型对照组,每组32只。DSS法构建IBD模型后,高、中、低治疗组分别予以Bortezomib溶液1.0 mg/kg、0.6 mg/kg、0.2 mg/kg腹腔注射,对照组予以PBS腹腔注射。分别于用药开始前、用药后1 d、3 d、7 d观察疾病活动指数(disease activity index,DAI)、组织学评分,ELISA法测定肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的血清水平;EMSA法评估核NF-κB p65与DNA结合的活性。结果造模后,小鼠DAI、组织学评分、TNF-α水平和NF-κB p65活性均较正常对照组显著降低,而应用Bortezomib治疗后,NF-κB p65活性显著受到抑制,TNF-α水平均逐渐降低,且DAI、组织学评分也均显著降低,具有明显的时间和剂量依赖性。结论 Bortezomib对小鼠结肠炎动物模型具有保护作用,可能通过抑制NF-κB的活性,下调TNF-α的表达发挥作用。随着Bortezomib治疗剂量和治疗天数的增加,对NF-κB的活性抑制作用越来越明显,对IBD的治疗作用也越来越来明显。Objective To observe whether or not Bortezomib by inhibiting the activity of nuclear factor-κB（NF-κB）can play a role in the treatment of inflammatory bowel disease（ IBD）. Methods Mice were challenged with drinking water containing 30 g/L dextran sulfate sodium（ DSS） for 7 consecutive days and then intraperitoneally treated with three doses of Bortezomib（0. 2,0. 6,or 1 mg/kg） for 1-,3-or 7-day,respectively. Mice in normal control and DSS groups were given the equivalent volume of PBS. DAI score,histological score and serum levels of TNF-α were observed. The expression levels of NF-κB p65 were evaluated by EMSA. Results DAI score,histological score,TNF-αand NF-κB p65 activity in mice with IBD were significantly lower than those in normal control group. After treatment with Bortezomib,the NF-κB p65 activity was significantly suppressed,the level of TNF-α was gradually reduced,the DAI,histological score were all down-regulated,and had obvious time and dose dependent. Conclusion These findings demonstrate that Bortezomib exerts a protective effect on DSS-induced colitis in experimental mousemodels,probably by inhibiting DNA binding activity of NF-κB,down-regulating the expression levels of TNF-α. With the increase of Bortezomib dose and treatment days,the inhibitory effect on NF-κB activity is more and more obvious,and the therapeutic effect on IBD is also more and more obvious.

关 键 词：硼替佐米 炎症性肠病 NF-ΚB 

分 类 号：R574[医药卫生—消化系统]