摘要
目的研究辛伐他汀对低氧条件下大鼠肺动脉平滑肌细胞胶原生成的影响和机制。方法在低氧条件下,以培养的大鼠肺动脉平滑肌细胞为模型,以3H-脯氨酸掺入法测定胶原合成,观察不同浓度辛伐他汀对大鼠肺动脉平滑肌细胞胶原合成的影响,同时测定平滑肌细胞内转化生长因子β1(TGF-β1)mRNA的表达及培养液中超氧化物歧化酶活性、丙二醛的含量,比较分析加入不同剂量辛伐他汀后上述指标的变化和相互关系。结果低氧组的平滑肌细胞3H-脯氨酸掺入量显著高于常氧组(P<0.01),不同剂量辛伐他汀组的平滑肌细胞3H-脯氨酸掺入量显著低于低氧组,但仍高于常氧组;低氧组TGF-β1mRNA的表达明显高于常氧组(P<0.01),辛伐他汀呈剂量依赖性抑制缺氧刺激的TGF-β1mRNA表达,其中辛伐他汀(10-6mol/L)组中TGFβ1mRNA表达抑制了55%(P<0.01),辛伐他汀(10-5mol/L)组则抑制了70%(P<0.01)。与常氧组相比,低氧组超氧化物歧化酶活性显著降低(P<0.01),而过氧化产物丙二醛显著升高(P<0.01)。辛伐他汀呈剂量依赖性地提高超氧化物歧化酶活性,抑制过氧化产物丙二醛的产生。结论辛伐他汀对缺氧条件下血管平滑肌细胞胶原合成具有抑制作用,并呈剂量依赖关系,其作用可能与抑制氧化应激及TGF-β1表达有关。
Objective To investigate the effects of simvastatin on the collagen synthesis of rat pulmonary arterial smooth muscle ceils （PASMCs） induced by hypoxia. Methods Under hypoxie condition, rat PASMCs were cultured with different concentrations of simvastatin. Collagen synthesis of PASMCs with or without simvastatin were measured by ^3H-proline incorporation assay. The mRNA expression of TGF-β1 and the contents of super oxide dismrtase （SOD） ,malondialdehyde （MDA） in medium were also measured. Results The incorporation data of ^3H-TdR in the hypoxia group was significantly increased as compared with that in the control group （P 〈 0.01）, and simvastatin significantly reduced the incorporation data of ^3H-TdR induced by hypoxia. The expression of TGF-β1 mRNA in the hypoxia group was significantly increased as compared with that in the control group （ P 〈 0. 01 ）, and simvastatin could significantly inhibited hypoxia-indueed expression of TGF-β1 mRNA in a dose-dependent manner. Compared with the hypoxia group,the expression of TGF-β1 mRNA decreased by 55% in simvastatin（ 10^-6mol/L） group （P 〈 0. 01 ）, and by 70% （ P 〈 0. 01 ） in simvastatin （ 10^-5mol/L） group. Compared with the control group, the activity of SOD was reduced and the contents of MDA were increased significantly in the hypoxia group. Simvastatin can increase the activity of SOD and reduced the content of MDA in a dose-dependent manner. Conclusions Simvastatin can decreases collagen synthesis of PASMCs. This effect might be explained that simvastatin can reduce lipid peroxide and expression of TGF-β1 mRNA.
出处
《中国呼吸与危重监护杂志》
CAS
2013年第3期300-303,共4页
Chinese Journal of Respiratory and Critical Care Medicine
关键词
低氧性肺动脉高压
肺动脉平滑肌细胞
辛伐他汀
胶原合成
Hypoxic pulmonary hypertension
Pulmonary arterial smooth muscle cells
Simvastatin
Collagen synthesis
