氟伐他汀对大鼠肺动脉高压的预防作用及对Caveolin-1表达的影响

目的:观察氟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:98只Wistar大鼠被随机分为3组:M+F组大鼠首先给予野百合碱(MCT,30 mg/kg)皮下注射和氟伐他汀(1 mg/kg)灌胃,每日各1次,连续2周,自第2周末至第6周末继续按氟伐他汀初始给药方案灌胃而不再进行MCT皮下注射。MCT组大鼠给予每日1次MCT(30 mg/kg)皮下注射,每日1次,且自第1周开始至第6周末给予同氟伐他汀等体积的生理盐水灌胃,每日1次。Saline组给予生理盐水皮下注射或灌胃。自实验开始间隔2周测定各组大鼠平均肺动脉压(mPAP)、右心室肥厚指数(RVHI)及肺组织caveolin-1蛋白相对含量。结果:MCT组大鼠实验第4周末mPAP和RVHI值均较Saline组显著增高。M+F组大鼠至第6周末才出现mPAP明显升高,但观察期间该组大鼠RVHI与Saline组比较差异无统计学意义。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),至第4周末和第6周末,caveolin-1表达进一步下调,而M+F组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形成的重要原因,氟伐他汀预防大鼠肺动脉高压形成的机制与其抑制caveolin-1表达下调有关。

Preventive Effects of Fluvastatin on Experimental Pulmonary Arterial Hypertension and Caveolin-1 Expression in Rats

Objective:To investigate the preventive effect of fluvastatin on experimental pulmonary arterial hypertension(PAH),and to explore the possible relations between caveolin-1 and PAH in rats.Methods:A total of 98 rats were randomly distributed into three groups as M+F group,treated with monocrotaline(MCT,30 mg/kg subcutaneous injection for one week) plus fluvastatin(1 mg/kg per day by gavage for six weeks),MCT group,treated only with MCT plus normal saline,and saline group,treated with normal saline.Mean pulmonary arterial pressure(mPAP),right ventricular hypertrophy index(RVHI) and caveolin-1 protein expressions were detected every two weeks during the six weeks' observation.Results:In week 4,mPAP and RVHI in MCT group were significantly higher than those of saline group.However,difference between M+F group and saline group in mPAP was observed until week 6,and no difference was observed in RVHI among the three groups during 6-week period.A significantly downregulated caveolin-1 expression was observed in week 2.Further extremely significant downregulation of caveolin-1 expression was observed in the following 4 weeks.No significant downregulation of caveolin-1 was observed in M+F group within 6 weeks.Conclusion:The downregulation of caveolin-1 expression is an important trigger for the induction of PAH.The effect of fluvastatin protecting against the formation of experimental pulmonary arterial hypertension correlates with caveolin-1 inhibition in rats.