阿托伐他汀通过过氧化体增殖物激活型受体γ促进一氧化氮生成抑制炎性因子产生
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Expression of PPARγ in Human Umbilical Vein Endothelial Cell and the Effect of Atorvastatin
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    摘要:

    目的观察阿托伐他汀是否能通过激活人脐静脉内皮细胞的过氧化体增殖物激活型受体γ从而改善血管内皮功能。方法将体外培养的人脐静脉内皮细胞的实验分为两部分,实验一分组:①对照组;②脂多糖组(1.0 mg/L);③阿托伐他汀1.0 mmol/L组;④脂多糖+阿托伐他汀1.0 mmol/L组;⑤脂多糖+阿托伐他汀5.0mmol/L组,经孵育24 h后,收集细胞和培养上清液,用RT-PCR方法测定不同浓度阿托伐他汀对人脐静脉内皮细胞的过氧化体增殖物激活型受体γ表达的影响,并用硝酸还原酶法测定不同浓度阿托伐他汀干预对脂多糖诱导后细胞培养上清液中的一氧化氮生成的影响,ELISA方法测定细胞培养上清液中人可溶性细胞间黏附分子含量的影响。实验二分组:①对照组;②阿托伐他汀5.0 mmol/L组;③0.2 mmol/L GW 9662组;④脂多糖+阿托伐他汀5.0mmol/L组;⑤GW 9662+脂多糖+阿托伐他汀5.0 mmol/L组,观察过氧化体增殖物激活型受体γ特异性阻断剂GW 9662对阿托伐他汀与脂多糖共同作用后人脐静脉内皮细胞的过氧化体增殖物激活型受体γ表达及培养上清液中一氧化氮、人可溶性细胞间黏附分子1含量变化的影响。结果不同浓度阿托伐他汀可上调人脐静脉内皮细胞的过氧化体增殖物激活型受体γ表达,且随着药物浓度的增加其上调受体表达的作用增强。不同浓度阿托伐他汀可干预脂多糖诱导的人脐静脉内皮细胞液中一氧化氮生成减少及人可溶性细胞间黏附分子1含量的增加,且随着药物浓度的增加上述作用增强。过氧化体增殖物激活型受体γ特异性阻断剂GW 9662可部分阻断阿托伐他汀上述作用。结论阿托伐他汀可能部分通过激活人脐静脉内皮细胞的过氧体增殖物激活型受体γ受体,促进一氧化氮生成,抑制炎性因子的产生,改善血管内皮功能。

    Abstract:

    Aim To investigate whether atorvastatin can improve the endothelial function through activating peroxisome proliferator-activated receptor gamma in human umbilical vein endothelial cells. Methods Human umbilical vein endothelial cells were cultured in vitro.And the 2~4 generation were used.Experiment 1: ①control group;②lipopolysaccharide group(1.0 mg/L);③atorvastatin 1.0 group(atorvastatin 1.0 mmol/L);④lipopolysaccharide+atorvastatin 1.0 group(atorvastatin 1.0 mmol/L);⑤lipopolysaccharide+atorvastatin 5.0 group(atorvastatin 5.0 mmol/L).After human umbilical vein endothelial cells were incubated with different concentrations of atorvastatin and lipopolysaccharide for 24 hours,the expression of Peroxisome proliferator-activated receptor gamma of human umbilical vein endothelial cells were evaluated with reverse transcription-polymerase chain reaction.The content of nitric oxide,soluble intracellular adhesion molecule-1 in cell culture fluid were measured with Nitrate reductase and ELISA.Experiment 2: ①control group;②atorvastatin 5.0 group(atorvastatin 5.0 mmol/L);③GW9662 group(GW9662 0.2 mmol/L);④lipopolysaccharide+atorvastatin 5.0 group(atorvastatin 5.0 mmol/L);⑤GW9662+lipopolysaccharide+atorvastatin group 5.0 group(GW9662 0.2 mmol/L,atorvastatin 5.0 mmol/L).After human umbilical vein endothelial cells were incubated with atorvastatin,lipopolysaccharide and GW9662(the specific inhibitor of peroxisome proliferator-activated receptor gamma) for 24 hours,the expression of Peroxisome proliferator-activated receptor gammain human umbilical vein endothelial cells were evaluated with RT-PCR.The content of nitric oxide,soluble intracellular adhesion molecule-1 in cell culture fluid were determined with the way of Nitrate reductase and ELISA. Results The expression of Peroxisome proliferator-activated receptor gamma of human umbilical vein endothelial cells were upregulated by different concentrations of atorvastatin.The expression reinforced with the increased concentration of atoravastatin.Compared with control group,the contents of nitric oxide significantly increased and soluble intracellular adhesion molecule-1 decreased in cell culture fluid when Human umbilical vein endothelial cells were incubated with lipopolysaccharide+atorvastatin 1.0 mmol/L and lipopolysaccharide+atorvastatin 5.0 mmol/L.The effects reinforced with the increased concentration of atorvastatin.The effects of atorvastatin are partially inhibited by GW9662(the specific inhibitor of peroxisome proliferator-activated receptor gamma). Conclusion The endothelial function was improved by atorvastatin partially through activating Peroxisome proliferator-activated receptor gamma.

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路岩,姜一农.阿托伐他汀通过过氧化体增殖物激活型受体γ促进一氧化氮生成抑制炎性因子产生[J].中国动脉硬化杂志,2009,17(11):893~896.

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  • 收稿日期:2009-08-11
  • 最后修改日期:2009-10-12
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