中文摘要：

目的：观察氟西汀对野百合碱（MCT）所致的大鼠肺动脉高压（PAH）的近期和远期疗效及伴随的病理生理学变化。方法：实验分为氟西汀持续干预组（M＋F组）、氟西汀短期干预组（M/F组）、MCT组及生理盐水组,共196只大鼠。其中前3组均先行MCT（60mg/kg）皮下注射3周造模,M＋F组为氟西汀（10mg/kg）干预9周,M/F组氟西汀干预3周。实验总共观察12周,分别于不同时间点观察大鼠肺组织形态学变化,并对肺动脉压（PAP）、管壁厚度百分比（PWT）、右心室肥厚指数（RVHI）及5-羟色胺转运体（5-HTT）的表达情况进行测定,并进行生存分析。结果：①M/F组大鼠在氟西汀停药后6周出现显著的肺血管重构和右心室肥厚,提示肺动脉高压复发,而M＋F组大鼠未观察到肺动脉高压复发及右心室肥厚加重;②M/F组5-HTT蛋白水平在氟西汀撤药后逐渐升高,且与肺动脉高压的严重程度相平行,而M＋F组在氟西汀撤药后未出现5-HTT表达增加。结论：①氟西汀能有效逆转MCT诱导的大鼠肺血管重构并改善右心室肥厚,且这一作用主要与氟西汀抑制5-HTT表达上调有关;②氟西汀长期持续干预较短期干预能更有效提高PAH大鼠的生存率。

英文摘要：

Objective：To investigate the short-term and long-term therapeutic effects of fluoxetine on monocrotaline-induced pulmonary arterial hypertension（PAH） and associated pathophysiologic alterations in PAH models.Methods：A total of 196 rats were randomly distributed into three groups.Long-term fluoxetine treatment group（M＋F,n=62） received a single subcutaneous injection of monocrotaline（MCT,60 mg/kg） for three weeks and then were treated with fluoxetine（10 mg/kg） once daily by gavage in the following nine weeks.Short-term fluoxetine treatment group（M/F,n=70） were treated with fluoxetine only for three weeks.The third group（MCT,n=46） were treated only with normal saline.The fourth group（Saline,n=18） was a normal control group.Morphometric changes,pulmonary arterial pressure（PAP）,percent wall thickness（PWT）,right ventricular hypertrophy index（RVHI）,and serotonin transporter（5-HTT） expressions were detected at various times during the 12-week observation;furthermore,survival analysis in each group was also performed until week 12.Results：①A recurrence of the completely reversed PAH and aggravation of right ventricular hypertrophy was observed six weeks after fluoxetine withdrawal in M/F group,while no signs of such a recurrence and aggravation was observed in M＋F group;②5-HTT protein levels were significantly raised in M/F group after fluoxetine discontinuation,which was paralleled with the severity of PAH;however,no upregulation of 5-HTT was found in M＋F group.Conclusion：Fluoxetine is effective in reversing MCT-induced pulmonary vascular remodeling and ameliorating right ventricular hypertophy in rats,which is associated with inhibition of overexpression of 5-HTT.Continuous fluoxetine administration is more effective than short-term administration in prolonging survival in rats with PAH.