罗格列酮对血管紧张素Ⅱ诱导血管平滑肌细胞血管紧张素Ⅱ受体表达的影响
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东南大学国家自然基金预研项目(XJ0690260)


Effects of Rosiglitazone on the Expression of Angiotensin Ⅱ Type 1 Receptor and Type 2 Receptor in Angiotensin Ⅱ-Induced Mice Vascular Smooth Muscle Cells
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    目的探讨罗格列酮对血管紧张素Ⅱ诱导血管平滑肌细胞血管紧张素Ⅱ受体表达的影响及抗动脉粥样硬化可能的分子机制。方法体外培养SD大鼠血管平滑肌细胞,应用半定量逆转录聚合酶链反应和免疫组织化学技术,测定罗格列酮对血管紧张素Ⅱ诱导大鼠血管平滑肌细胞血管紧张素Ⅱ1型受体和2型受体mRNA和蛋白表达的剂量、时间依赖的影响。结果基础状态下,血管平滑肌细胞血管紧张素Ⅱ1型受体和2型受体均有少量的表达。血管紧张素Ⅱ显著上调血管紧张素Ⅱ1型受体(p<0.01)和下调2型受体的表达(p<0.05)。浓度依赖实验表明,不同浓度罗格列酮(20、30和50μmol/L)干预12h均显著下调血管紧张素Ⅱ1型受体mRNA和蛋白的表达(p<0.01),上调2型受体mRNA和蛋白的表达(p<0.01和0.05)。时间依赖实验表明,30μmol/L的罗格列酮干预后,6h即出现明显的干预效应,24h时下调血管紧张素Ⅱ1型受体和上调2型受体mRNA和蛋白的作用最大,与血管紧张素Ⅱ组比差异有显著性(p<0.01)。结论罗格列酮可呈浓度依赖和时间依赖性地下调血管紧张素Ⅱ诱导的大鼠血管平滑肌细胞血管紧张素Ⅱ1型受体mRNA和蛋白的表达,上调血管紧张素Ⅱ2型受体mRNA和蛋白的表达,这可能是过氧化体增殖物激活型受体γ激动剂罗格列酮发挥抗炎、抗动脉粥样硬化作用的重要机制。

    Abstract:

    Aim To investigate the effects of rosiglitazone on the expression of angiotensin Ⅱ(AngⅡ)type 1 receptor(AT1R)and AngⅡ type 2 receptor(AT2R)in AngⅡ-induced vascular smooth muscle cells(VSMC)and possible molecular mechanisms of anti-atherosclerosis.Methods VSMC of mice were cultured by the explant-attachment method.Using semi-quantitative reverse transcription polymerase-chain reaction(RT-PCR)and immunochemistry,we measured the dose and time dependent effects of rosiglitazone on AT1R and AT2R mRNA and protein in AngⅡ-induced mice VSMC.Results Slight expressions of AT1R and AT2R were observed in cultured VSMC in vitro.AngⅡmarkedly upregulated the expression of AT1R mRNA and protein(p<0.01).Meanwhile,AngⅡdownregulated the expression of AT2R mRNA and protein(p<0.01 and 0.05).Twelve hours post different concentration rosiglitazone(20,30,50 μmol/L)treatment,the expression of AT1R mRNA and protein of VSMC were significantly attenuated(p<0.01,vs AngⅡ group).However,the expression of AT2R mRNA and protein of VSMC were markedly upregulated(p<0.01,vs AngⅡ group).At 6 hours post 30 μmol/L rosiglitazone treatment,the expression of AT1R mRNA and protein decreased,and then the expression of AT2R mRNA and protein increased,reaching a maximum at 24 h post treatment(p<0.01).Conclusions Rosiglitazone can not only downregulate the expression of AT1R mRNA and protein,but also upregulate the expression of AT2R mRNA and protein in AngⅡ-induced VSMC in concentration-dependent and time-dependent manners.Above effects may be crucial mechanisms of the anti-inflammation and anti-atherosclerosis of peroxisome proliferator-activated receptor-γ agonists.

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任利群,郭晓珍,李荧娟,李艳志,刘乃丰.罗格列酮对血管紧张素Ⅱ诱导血管平滑肌细胞血管紧张素Ⅱ受体表达的影响[J].中国动脉硬化杂志,2007,15(1):35~39.

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  • 收稿日期:2006-10-16
  • 最后修改日期:2007-01-12
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