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-  2015 

辛伐他汀对大鼠实验性肺动脉高压的预防作用 Protective Effect of Sinvastatin Against Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats

Keywords: 辛伐他汀,肺动脉高压,Caveolin-1,野百合碱

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Abstract:

目的:观察辛伐他汀对大鼠实验性肺动脉高压(PAH)的预防作用,并探讨Caveolin-1与PAH的关系。方法:85只Wistar大鼠被随机分为3组:M+S组大鼠首先给予野百合碱(MCT,5mg/kg)皮下注射和辛伐他汀(1mg/kg)灌胃,每日各1次,连续2周,自第2周末至第6周末继续按辛伐他汀初始给药方案灌胃而不再进行MCT皮下注射。MCT组实验前2周给予每日1次MCT(5mg/kg)皮下注射,且自第1周开始至第6周末持续给予同辛伐他汀等体积的0.9%盐水灌胃。对照组组自实验开始至实验第6周给予同辛伐他汀等体积的0.9%盐水灌胃,此外,实验前2周给予同MCT等体积的0.9%盐水皮下注射。自实验开始,间隔2周对各组大鼠进行体循环动脉压(SAP)、右心室收缩压(RVSP)、右心室肥厚指数(RVHI)及Caveolin-1表达水平进行测定,实验总共观察6周。结果:MCT组大鼠实验第4周末RVSP和RVHI分别为(23.5±1.9)mmHg和0.31±0.02,均较对照组显著增高。而M+S组大鼠至第6周末才出现RVSP明显升高,但观察期间该组大鼠RVHI与对照组无统计学差异。MCT组大鼠实验第2周末Caveolin-1蛋白相对含量较Saline组显著降低(P<0.05),且在随后4周内表达进一步下调,而M+S组在实验6周内未观察到有统计学意义的Caveolin-1表达下调。结论:Caveolin-1表达下调是大鼠实验性PAH形成的重要伴随特征之一,辛伐他汀对大鼠实验性肺动脉高压具有预防作用,该机制与其抑制Caveolin-1表达下调有关

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