雷公藤内酯醇抑制TNF-α表达对小鼠溃疡性结肠炎的影响  

Effect of inhibition of TNF-α expression by triptolide on experimental ulcerative colitis in mice

作　　者：张海峰[1] 张彬[1] 周国雄[1] 陈卫昌[2] Hai-feng Zhang;Bin Zhang;Guo-xiong Zhou;Wei-chang Chen(Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China;The First Affiliated Hospital of Soochow University,Suzhou,Jiangsu 215006,China)

机构地区：[1]南通大学附属医院,江苏南通226001 [2]苏州大学附属第一医院,江苏苏州215006

出　　处：《中国现代医学杂志》2018年第20期6-13,共8页China Journal of Modern Medicine

基　　金：江苏省南通市社会发展基金(No:BK2012074)

摘　　要：目的了解雷公藤内酯醇(TL)对葡聚糖硫酸钠(DSS)致溃疡性结肠炎(UC)小鼠的疗效,探索其是否与抑制肿瘤坏死因子-α(TNF-α)过表达相关。方法复制DSS致UC小鼠动物模型,分为空白对照组、生理盐水组、丙二醇组、地塞米松组、美莎拉嗪组,以及TL 1、2、3组。分别予以3种剂量的TL,以及美沙拉嗪、地塞米松治疗,观察小鼠疾病活动指数、结肠组织学评分、结肠病理学评分,检测TNF-α在血清和局部病变组织中的表达变化。结果 TL组、地塞米松组、美莎拉嗪组小鼠结肠炎症状减轻,TNF-α表达下调。TL 2、3组及地塞米松组、美莎拉嗪组分别与生理盐水组、丙二醇组比较,差异有统计学意义(P<0.05)。结论 TL对UC有治疗作用,可能是通过抑制TNF-α过表达发挥作用,提示TL可能是一种有效的治疗UC的方法。Objective To investigate the effect of triptolide(TL)on ulcerative colitis(UC)and explore the potential association between therapeutic effect of TL and TNF-αexpression using dextran sulfate sodium salt(DSS)mouse model.Methods The DSS mouse model was established to simulate human UC.Eighty BALB/c female mice were randomly allocated into eight groups with equal number.Group A was blank control group,the mice in group B received normal saline injection,the mice in group C received propylene glycol injection,the mice in group D was injected with Dexamethasone,the mice in group E was fed with water-dissolved Mesalazine through stomach tube at a daily dose of 20-30 mg/kg,and the mice in groups F,G and H were administered with different doses of TL(TL1,TL2 and TL3).Information regarding mice activity,diet and stool property was recorded daily.The mice were sacrificed on day 8,and disease activity index,colon tissue histological score,and colon pathological score were calculated.The serum level of TNF-αwas tested by ELISA,and TNF-αexpressions in the colonic mucosa specimens were examined by fluorescence quantitative PCR at gene level and by Western blot at protein level.Results In the TL(TL2 and TL3),Mesalazine and Dexamethasone-treated mice,the symptoms of colitis were relieved,TNF-αexpression was significantly decreased compared with the normal saline and propylene glycol injection groups(P<0.05).Conclusions TNF-αexpression is upregulated in UC mouse model and involved in the development and progression of UC.TL can inhibit TNF-αexpression,suggesting that TL may be a novel therapeutic drug for the treatment of UC.

关 键 词：溃疡性结肠炎 肿瘤坏死因子-Α 雷公藤内酯醇 治疗 动物实验 

分 类 号：R574.62[医药卫生—消化系统]