【摘要】 目的探讨匹伐他汀在防治肺动脉高压中的作用及其可能机制。方法雄性斯泼累格·多雷(SD)大鼠50只,随机分为5组(n=10),分别为正常对照组、模型对照组、匹伐他汀预防组(1 mg·kg-1·d-1)和匹伐他汀大剂量(3 mg·kg-1·d-1)治疗组、小剂量(1 mg·kg-1·d-1)治疗组。除正常对照组外,其余4组均通过皮下注射野百合碱55 mg·kg-1,诱导大鼠形成肺动脉高压。8周后,比较各组存活率、平均肺动脉高压(m PAP)、血小板源性生长因子-B(PDGFB)、Rac1mRNA的表达及白细胞介素-6(IL-6)分泌水平。结果匹伐他汀预防组、正常对照组大鼠均存活,匹伐他汀小剂量治疗组、大剂量治疗组与模型对照组小鼠存活率分别为60.0%,80.0%,40.0%(P<0.01);与模型对照组比较,匹伐他汀治疗组m PAP均降低(均P<0.01),肺组织PDGF-B表达、IL-6分泌及Rac1基因表达均降低(均P<0.01)。结论匹伐他汀可能是通过对Rac1基因和PDGF-B表达的调节以抑制肺动脉平滑肌细胞增殖和抑制IL-6分泌等机制防治肺动脉高压。更多还原

【Abstract】 Objective To investigate the effects and mechanism of pitavastatin on monocrotaline( MTC)-induced pulmonary arterial hypertension( PAH) in rats. Methods A total of 50 male Sprague-Dawley rats were randomly divided into five groups( n = 10 each) : pitavastatin treatment at low dose( 1 mg·kg-1·d-1),high dose( 3 mg·kg-1·d-1),pitavastatin prevention regimen( 1 mg·kg-1·d-1),the model control,and the normol control group. PAH was induced by applying a single subcutaneous injection of MTC( 55 mg·kg-1) in the first four groups of rats. The treatment lasted for 8 weeks. At the end of the study,survival rates and mean pulmonary arterial pressure( m PAP) among groups were compared. The expression levels of platelet-derived growth factor-B( PDGF-B) and IL-6,Rac1 mRNA in small pulmonary artery were also detected. Results All rats in the prevention protocol and normal control group survived. Pitavastatin treatment improved survival in the treatment protocol( P < 0. 01). The survival rate in the low dose,high dose,and model control group was 60. 0%,80. 0%,and 40. 0%,respectively. Pitavastatin in both prevention and treatment protocol significantly lowered m PAP( P < 0. 01). Pitavastatin also inhibited PDGF-B and IL-6 expression( P < 0. 01),and inhibited Rac1 mRNA expression in lung tissues( P < 0. 01).Conclusion Pitavastatin reduces m PAP in the MTC-induced PAH rat model,the mechanism of which may be related to inhibition of Rac1 expression,smooth muscle cell proliferation and inflammatory mediator IL-6.更多还原