摘要
目的:探讨溃疡性结肠炎大鼠β2AR-β-arrestin2-NF-κB信号转导通路及氧化苦参碱的干预作用.方法:SD♂大鼠40只随机分为正常对照组、模型组、美沙拉嗪组和氧化苦参碱组4组,每组10只.正常对照组未造模,其余3组大鼠均采用TNBS造模诱导实验性大鼠结肠炎.其中氧化苦参碱组大鼠予苦参素(氧化苦参碱)注射液肌肉注射,美沙拉嗪组大鼠予美沙拉嗪混悬液灌胃,模型组和正常组大鼠均以3mL蒸馏水灌胃.注意观察实验大鼠腹泻、便血症状.第7天,每组随机处死2只大鼠,比较各组结肠组织大体组织病理变化,取病变明显的结肠组织石蜡包埋切片并HE染色,镜下观察各组结肠病理组织学改变.第16天禁食24h后处死大鼠,用免疫组织化学技术和Western blot检测实验大鼠结肠组织和脾脏淋巴细胞β2肾上腺素受体(β2AR)、β-arrestin2和NF-κBp65表达的变化.结果:与正常对照组比较,模型组大鼠结肠黏膜组织及脾脏淋巴细胞NF-κBp65表达均显著上升(均P<0.01),β2AR和β-arrestin2表达均显著下降(均P<0.01).与模型组比较,美沙拉嗪组和氧化苦参碱组大鼠结肠黏膜组织NF-κBp65表达均显著下降(16.26±5.51,18.34±3.34vs61.90±17.75,均P<0.01),β2AR表达均显著上升(47.27±12.40,61.75±10.40vs12.20±2.70,均P<0.01),β-arrestin2表达均显著上升(70.71±12.84,76.14±8.77vs16.80±7.17,均P<0.01).与模型组比较,美沙拉嗪组和氧化苦参碱组大鼠脾脏淋巴细胞NF-κBp65表达均显著下降(114.23±11.56,145.62±13.05vs249.70±18.94,均P<0.01),β2AR表达均显著上升(1006.50±226.89,1102.11±297.72vs594.97±209.59均P<0.01),β-arrestin2表达均显著上升(189.97±21.12,162.04±15.69vs111.77±19.43,均P<0.01).但美沙拉嗪组和氧化苦参碱组之间比较β2AR、β-arrestin2、NF-κBp65表达无显著差异.结论:β2AR-β-arrestin2-NF-κB信号转导通路参与溃疡性结肠炎的病理过程,氧化苦参碱可以通过调节β2AR-β-arrestin2-NF-κB信号转导通
AIM：To investigate whether the β2-adrenoceptor（β2AR）-β-arrestin2-NF-κB signaling pathway mediates the therapeutic effects of oxymatrine on ulcerative colitis in rats.METHODS：Forty Sprague-Dawley rats were randomly and equally divided into four groups：normal control group,model group,mesalazine group and oxymatrine group.Experiment colitis was induced with TNBS in rats in each group except the normal control group.Therats in the oxymatrine group were intramuscularly injected with oxymatrine injection for 15 d,while those in the mesalazine group were lavaged with 3 mL mesalazine solution for the same duration.The rats in the normal control group and model group were lavaged with 3 mL water for 15 d.Diarrhea and bloody stools were carefully observed in experimental rats.Two rats in each group were randomly selected and executed on day 7 for observing colonic histological changes.On day 16,the remaining rats were executed after fasting 24 h to detect the expression of β2AR,β-arrestin2 and NF-κB p65 in colon tissue and splenic lymphocytes by immunohistochemistry and Western blotting,respectively.RESULTS：Compared with the normal control group,the expression of NF-κB p65 was significantly increased（both P 0.01） and the expression of β2AR and β-arrestin2 was significantly decreased（both P 0.01） in colonic mucosa and splenic lymphocytes in the model group.Compared with the model group,the expression of NF-κB p65 was significantly decreased（16.26 ± 5.51 and 18.34 ± 3.34 vs 61.90 ± 17.75,both P 0.01） and the expression of β2AR and β-arrestin2 was significantly increased in colonic mucosa in the mesalazine group and oxymatrine group（47.27 ± 12.40 and 61.75 ± 10.40 vs 12.20 ± 2.70,both P 0.01;70.71 ± 12.84 and 76.14 ± 8.77 vs 16.80 ± 7.17,both P0.01）.Compared with the model group,the expression of NF-κB p65 was significantly decreased（114.23 ± 11.56 and 145.62 ± 13.05 vs 249.70 ± 18.94,both P0.01） and the expression of β2AR and β-arrestin2 was significantly increased
出处
《世界华人消化杂志》
CAS
北大核心
2010年第22期2308-2316,共9页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
No.30772878~~
