西地那非和辛伐他汀联合治疗可改善野百合碱诱导的大鼠肺动脉高压。
Combination of sildenafil and simvastatin ameliorates monocrotaline-induced pulmonary hypertension in rats.
机构信息
Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital and Beijing Institute of Respiratory Medicine, Capital Medical University, Beijing, China.
出版信息
Pulm Pharmacol Ther. 2010 Oct;23(5):456-64. doi: 10.1016/j.pupt.2010.02.003. Epub 2010 Feb 23.
Sildenafil, a phosphodiesterase-5 inhibitor, and simvastatin, a cholesterol lowering drug, both have therapeutic effects on PAH; however, the combination of these drugs has not been tested in the treatment of PAH. The purpose of this study was to determine whether the combination of sildenafil and simvastatin is superior to each drug alone in the prevention of MCT-induced PAH. Phosphorylated Smad levels were decreased in lung tissue in MCT-injected rats, whereas ERK protein levels were increased. This indicates a possible role for an increase in mitogenic ERK activity in addition to decreased proapoptotic Smad signaling in the MCT model of PAH. Combination sildenafil and simvastatin treatment prevented the MCT-induced increases in right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH), exerted an anti-proliferative effect on pulmonary artery smooth muscle cells (PASMC). Our results indicate that combination therapy with sildenafil and simvastatin attenuated the development of pulmonary hypertension more than either treatment alone.
西地那非是一种磷酸二酯酶-5 抑制剂，辛伐他汀是一种降胆固醇药物，两者均对 PAH 有治疗作用；然而，尚未在 PAH 治疗中测试这两种药物的联合应用。本研究旨在确定西地那非和辛伐他汀联合应用是否优于两种药物单独应用预防 MCT 诱导的 PAH。在 MCT 注射大鼠的肺组织中，磷酸化 Smad 水平降低，而 ERK 蛋白水平增加。这表明在 MCT 诱导的 PAH 模型中，除了促凋亡 Smad 信号的减少之外，有丝分裂原 ERK 活性的增加可能起作用。联合西地那非和辛伐他汀治疗可预防 MCT 诱导的右心室收缩压（RVSP）和右心室肥厚（RVH）升高，对肺动脉平滑肌细胞（PASMC）具有抗增殖作用。我们的结果表明，与单独治疗相比，西地那非和辛伐他汀联合治疗可更有效地减轻肺动脉高压的发展。
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