氧化苦参碱干预IκB-α蛋白对溃疡性结肠炎的治疗作用机制研究  

Study on Mechanism of Oxymatrine in Treatment of Ulcerative Colitis in Rats

作　　者：熊永爱[1] 韩丽[1] 王淼[1] 苏娟[1] 

机构地区：[1]成都中医药大学药学院,成都611137

出　　处：《中国实验方剂学杂志》2012年第8期152-155,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重大科技专项经费(重大新药创制专项)(2009ZX09103-307)

摘　　要：目的:研究氧化苦参碱抗溃疡性结肠炎作用机制。方法:SPF级大鼠随机分成正常组、UC模型组、氧化苦参碱+UC模型组(ig给予氧化苦参碱180 mg·kg-1)、柳氮磺胺吡啶+UC模型组(ig给予柳氮磺胺吡啶600 mg·kg-1)。采用2,4,6-三硝基苯磺酸(TNBS)致大鼠溃疡性结肠炎症,连续给药21 d。实验结束后,剖取结肠病灶组织,采用免疫组织化学方法检测各组动物结肠组织细胞中核转录因子κB(NF-κB)的抑制蛋白(IκB-α)蛋白阳性细胞表达率,同时测定每组动物结肠组织中肿瘤坏死因子-α(TNF-α),白介素(interleukin,IL)1β(IL-1β),IL-6,IL-8细胞因子表达,并对每只动物结肠病理切片做显微镜检查。结果:氧化苦参碱组动物结肠黏膜细胞中IκB-α阳性细胞表达率21.8%±5.0%,显著低于模型组(25.6%±2.9%)(P<0.01);结肠细胞中TNF-α(66.23±2.64)pg·mg-1,IL-1β(149.42±64.69)pg·mg-1,IL-6(668.83±98.11)pg·mg-1和IL-8(91.83±23.14)pg·mg-14种细胞因子的表达率较模型组相比也显著降低(P<0.01);结肠组织显微镜检查,治疗组动物结肠细胞炎症、淋巴细胞浸润、黏膜损伤修复率明显高于模型组。结论:氧化苦参碱通过干预IκB-α蛋白表达,进而抑制溃疡性结肠炎症细胞中核转录因子κB(NF-κB)活性,产生抗炎效果。Objective：To study the mechanism of oxymatrine treating ulcer colitis（UC）in rats.Method： SPF rats were randomly divided into normal group,UC model group,oxymatrine ＋UC group（oxymatrine 180 mg·kg-1,ig）,sulfasalazine＋UC model group（sulfasalazine 600 mg·kg-1,ig）,2,4,6-trinitrobenzene sulfonic acid（TNBS） was used to induce rat ulcer colitis model,and corresponding drugs were given for 21 d.after 21 days of administration,colitis were collected,immunohistochemistry method was used to detect expression of κBα（IκB-α） protein in colon tissue,while the expression of tumor necrosis-factor-α（TNF-α）,interleukin（IL）-1β,IL-6,IL-8 cytokines were measured in each colonic tissue,and microscopic examination of colonic biopsy were carried out.Result： IκB-α protein expressions in oxymatrine group 21.8%±5.0% was significantly lower than that of model group 25.6%±2.9%（P0.01）;and the expressions of TNF-α（66.23 ±2.64）pg·mg-1,IL-1β（149.42 ±64.69）pg·mg-1,IL-6（668.83±98.11）pg·mg-1and IL-8（91.83±23.1 4） pg·mg-1was significantly decreased（P0.05）,compared with model group.Microscopic examination of colon tissue showed that the colonic inflammation,lymphocyte infiltration,mucosal damage in treatment group were significantly better than these of model group.Conclusion： Oxymatrine has anti-inflammatory effect by interfering with the IκB-α protein expression,and inhibiting the nuclear transcription factor κB（nuclear transcription factor-kappaB,NF-κB） activity in colitiscells.

关 键 词：氧化苦参碱 溃疡性结肠炎 κB抑制蛋白α 核转录因子ΚB 

分 类 号：R285.5[医药卫生—中药学]