氟伐他汀对肺动脉高压大鼠5-羟色胺转载体表达的影响

Effect of fluvastatin on serotonin transporter expression in rats with pulmonary arterial hypertension

目的观察氟伐他汀对野百合碱（MCT）所致的肺动脉高压大鼠肺组织5-羟色胺转载体（5-HTT）表达的影响。方法62只大鼠随机分为3组：①M＋F组：大鼠首先给予MCT（40 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。第3~6周继续按氟伐他汀初始给药方案灌胃,不再进行MCT皮下注射。②MCT组：实验前2周给予MCT（40 mg/kg）1次/d皮下注射,第3~6周末给予同氟伐他汀等体积的0.9%盐水灌胃 ③Saline组：分别于实验前2周及第3~6周给予等体积的盐水皮下注射和灌胃。分别于不同时间点,对大鼠的血流动力学及相关参数和5-HTT的表达情况进行测定。结果MCT组大鼠于实验第2周末即出现显著的肺动脉高压伴5-HTT蛋白水平异常增高,且在观察期间逐渐增高。M＋F组大鼠第6周末出现肺动脉压异常增高,但未伴5-HTT表达增高。结论氟伐他汀能有效抑制5-HTT表达上调,该作用可能与其对大鼠肺动脉高压的抑制作用有关。

Objective To investigate the effect of fluvastatin on serotonin transporter expression in rats with pulmonary arterial hypertension. Methods 62 rats were randomly divided into 3 groups. One group （ M ＋ F, n = 26） received 2-week subcutaneous injection of MCT （40 mg/kg, qd） with a continuous administration of fluvastatin （1 mg/kg） once a day by garage for 6 weeks. Another group （MCT,n =26） received a single subcutaneous injection of MCT （40 mg/kg） in the first 2 weeks,and then were given an equivalent volume of saline garage from 15th day to 42nd day. The third group （ Saline,n = 10） received a 2-week equivalent volume of 0.9% saline injection and a 4-week saline gavage,respectively. Pulmonary arterial pressure （PAP） and serotonin transporter （5-HTT） protein expressions were detected at various time during the 6-week observation. Results Rats in MCT group presented with dramatic PAH together with overexpression of 5-HTT protein at 14th day , which went further in the observation;however,only mild PAIl was observed in M ＋ F group without upregulation of 5-HTT protein at 42nd day. Conclusion Fluvastatin can effectively inhibit overexpression of 5-HTT protein in MCT-induced hypertension, it could possibly correlate with the preventive effect of fluvastatin on rats with pulmonary arterial hypertension.