白藜三醇对黄嘌呤—黄嘌呤氧化酶致平滑肌细胞核因子-κB活化及蛋白激酶Cα表达的干预
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Intervention of Resveatrol on Activated Nuclear Factor-κB and Expression of Protein Ki- nase Cα Induced by Xanthine and Xanthine Oxidase in Cultured Rabbit Aortic Smooth Muscle Cells
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    摘要:

    为探讨红葡萄酒的最有效成分之一白藜三醇拮抗黄嘌呤—黄嘌呤氧化酶对血管平滑肌细胞内核因子活性和蛋白激酶Ca表达的影响,以培养幼兔主动脉平滑肌细胞为研究对象,分别给予不同剂量的黄嘌呤—黄嘌呤氧化酶和/或白藜三醇,采用噻唑蓝法、电泳迁移率改变分析法、免疫组织化学和原位杂交技术检测不同处理组平滑肌细胞增殖及核因子的活性和蛋白激酶Ca蛋白及其mRNA的表达变化。结果发现,不同浓度黄嘌呤—黄嘌呤氧化酶的系统所产生的氧自由基可明显增加体外培养血管平滑肌细胞增殖及核因子的活性和蛋白激酶蛋白Ca及其mRNA的表达水平,白藜三醇呈剂量依赖性的抑制氧自由基对体外培养血管平滑肌细胞的增殖作用和核因子的活性,并下调蛋白激酶Ca的表达水平;其中以终浓度100μmol/L的白藜三醇对氧自由基介导的核因子活性的抑制作用最强,终浓度200μmol/L的白藜三醇对血管平滑肌细胞的增殖作用及蛋白激酶Ca表达的抑制作用最强。实验结果提示,红葡萄酒的有效成分白藜三醇可能是通过抑制核因子的诱导合成而阻断黄嘌呤—黄嘌呤氧化酶系统所产生氧自由基的促蛋白激酶Ca的表达效应,进而抑制平滑肌细胞增殖,发挥其抗动脉粥样硬化的作用。

    Abstract:

    Aim To investigate the effect of resveatrol in red wine on the activity of NF-κB and the expressions of protein kinase Co (PKCα) induced by xanthine and xanthine oxidase in cultured rabbit aortic smooth muscle cell (SMC). Methods At first we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide metabolism to study the proliferation, then detected activity of nuclear factor-κB (NF-κB) and the protein and mRNA expressions of protein kinase Ca (PKCα) by using electro-phoresis mobility shift assay (EMSA), immunohistochemistry and in situ hybridyzation in cultured rabbit aortic smooth muscle cells (SMC). Results 100 - 200 μmol/L resveatrol (RES), an effective composition in red wine, was confirmed to inhibit proliferation of smooth muscle cells. At same time, the activity of NF-κB as well as the protein and mRNA expressions of protein kinase Ca in rabbit aortic SMC, which were promoted by the oxygen free radicals induced by xanthine and xanthine oxidase, were inhibited. Conclusions Resveatrol may antagonize the increasing of NF-κB activity as well as protein and mRNA expressions of protein kinase Cμ indued by oxygen free radicals in cultured rabbit aortic smooth muscle cells, which may play an important role in preventing active oxygen species leision to atherosclerosis.

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崔华,何作云.白藜三醇对黄嘌呤—黄嘌呤氧化酶致平滑肌细胞核因子-κB活化及蛋白激酶Cα表达的干预[J].中国动脉硬化杂志,2003,11(7):617~621.

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  • 收稿日期:2003-02-27
  • 最后修改日期:2003-11-27
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