氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响

Involvement of Rho kinase activity in the protective effect of fluoxetine against monocrotaline-induced pulmonary arterial hypertension in rats

目的研究氟西汀对野百合碱诱导的肺动脉高压大鼠Rho激酶活性的影响。方法建立野百合碱-1-1诱导的肺动脉高压大鼠模型,将大鼠随机分为4组:对照组、野百合碱组、氟西汀低剂量(2mg·kg·d)组、-1-1氟西汀高剂量(10mg·kg·d)组。观察各组大鼠血流动力学与肺小动脉形态学的变化,Western blot方法检测ROCK1与ROCK2的蛋白表达,以及MYPT1的磷酸化。结果野百合碱诱导大鼠肺动脉压力升高、肺动脉重构、肺组织炎症反应,上调大鼠肺组织中ROCK1与ROCK2以及增加Rho激酶的活性;氟西汀剂量依赖地抑制这些改变。结论氟西汀抑制野百合碱诱导的大鼠肺动脉高压,与抑制Rho激酶活性有关。

Objective To study the involvement of Rho kinase（ROCK） activity in the protective effect of fluoxetine against monocrotaline-induced pulmonary arterial hypertension in rats. Methods Monocrotaline was applied to establish pulmonary arterial hypertension in rats. The rats were randomly divided into four groups： control group,-1-1 monocrotaline group, low-dose fluoxetine group（2mg· kg d）, and high-dose fluoxetine group（10）. The hemodynamics and morphology of pulmonary arterioles were determined, and the expression of ROCK were measured by Western blot. Results Monocrotaline promoted the increase of pulmonary arterial pressure, pulmonary arterial remodeling and lung inflammation, and upregulated ROCK1 and ROCK2 protein expression and MYPT1 phosphorylation. Fluoxetine inhibited these changes dose dependently. Conclusion The inhibition of Fluoxetine on monocrotaline-induced pulmonary arterial hypertension might be related to the dowregulation of ROCK activity.