β-arrestin1在实验性大鼠结肠炎发生机制中的作用及氧化苦参碱的干预作用  

Pathogenetic Mechanism of β-arrestin1 in Experimental Colitis of Rats and Intervention Effects of Oxymatrine

作　　者：廖奕[1] 范恒[1] 陈小艳[1] 张丽娟[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院中西医结合科,武汉430022

出　　处：《中国中西医结合杂志》2010年第10期1067-1072,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.30772878)

摘　　要：目的研究β-arrestin1在实验性大鼠结肠炎发生机制中的作用,δ阿片受体-β-arrestin1-Bcl-2信号转导通路是否参与实验性大鼠结肠炎的病理过程,氧化苦参碱(OMT)能否通过干预δ阿片受体-β-ar-restin1-Bcl2信号转导通路减轻实验性大鼠结肠炎。方法将26只SD大鼠随机分为4组:分别为正常对照组6只、模型组6只、美沙拉嗪组6只和OMT组8只。正常对照组未行造模,其余3组大鼠均采用三硝基苯磺酸(TNBS)造模。OMT组大鼠给予苦参素注射液肌肉注射,美沙拉嗪组大鼠给予美沙拉嗪混悬液灌胃,模型组和正常组大鼠均以蒸馏水3mL灌胃。治疗15天,观察实验大鼠结肠病理组织学改变,并分别用免疫组化和Western免疫印迹技术分别检测实验大鼠结肠黏膜组织和脾脏T淋巴细胞δ阿片受体、β-arrestin1和Bcl-2表达变化。结果与正常对照组比较,模型组δ阿片受体、β-arrestin1和Bcl-2表达明显增高(P<0.01)。与模型组比较,美沙拉嗪组和OMT组δ阿片受体、β-arrestin1、Bcl-2表达均显著下降(P<0.01)。结论δ阿片受体-β-arrestin1-Bcl-2信号转导通路参与TNBS诱导的实验性大鼠结肠炎的发病机制;OMT抑制δ阿片受体-β-arrestin1-Bcl-2信号转导通路,是OMT改善TNBS诱导的实验性大鼠结肠炎的机制之一。Objective To investigate the pathogenetic mechanism of β-arrestin1 in the rat＇s experimental colitis,whether the δ opioid receptor-β-arrestin1-Bcl-2 signal transduction pathway involves the pathological process of experimental colitis in rats,and whether oxymatrine could attenuate colitis through this pathway.Methods Twenty-six SD rats were randomly divided into four groups,the normal control group,the model group,the mesalazine treated group and the oxymatrine treated group（8 rats in the last group and 6 each in the others）.The colitis model was established with trinitrobenzene sulfonic acid（TNBS）,and rats in the latter two groups were treated by oxymatrine（intramuscular injection）and mesalazine（3 mL solution gavaged）for 15 days,respectively,while rats in the former two groups were fed with equal volume of distilled water.Symptoms of diarrhea and bloody stool as well as colonic patho-histologic changes were observed,and changes in expressions of δ opioid receptor,β-arrestin1 and Bcl-2 in rat＇s colon tissue and spleen T lymphocytes were detected with immuno-histochemistry and Western immuno-blotting techniques,respectively.Results In contrast to the normal control group,expressions of δ opioid receptor,β-arrestin1 and Bcl-2 were significantly higher in the model group（P0.01）;compared with the model group,they were significantly lower in the two treated groups（P0.01）.Conclusions δ opioid receptor-β-arrestin1-Bcl-2 signal transduction pathway participates in the pathogenesis of TNBS-induced experimental colitis in rats.Oxymatrine can intervene the signal transduction,which may be one of the mechanisms of oxymatrine in attenuating colitis in rats.

关 键 词：Δ阿片受体 β-arrestin1 Bcl-2 信号转导 CD4+T细胞 TNBS诱导的结肠炎 氧化苦参碱 

分 类 号：R574[医药卫生—消化系统]