中文摘要：

目的研究泛素羧基末端水解酶L1（UCH-L1）在氟西汀抑制野百合碱诱导的大鼠肺动脉高压中的作用。方法用野百合碱（60 mg·kg-1）建立肺动脉高压大鼠模型,用低剂量（2 mg·kg-1·d-1）或高剂量（10 mg·kg-1·d-1）的氟西汀进行干预,观察各组大鼠血流动力学,肺组织与肺小动脉形态,以及UCH-L1蛋白表达与核因子κB（NF-κB）核转位的变化。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、肺组织UCH-L1表达减少以及NF-κB活性增加。氟西汀剂量依赖地抑制这些变化。但是各组之间大鼠肺动脉UCH-L1蛋白表达差异无显著性。结论氟西汀抑制野百合碱诱导的大鼠肺组织炎症反应,与上调的UCH-L1蛋白抑制NF-κB活性有关。

英文摘要：

Aim To study the role of ubiquitin carboxyl terminal hydrolase L1（ UCH-L1） involved in the protective effect of fluoxetine against monocrotaline-induced pulmonary arterial hypertension in rats. Methods Monocrotaline（ 60 mg ·kg- 1） was used to establish pulmonary arterial hypertension in rats and lowdose（ 2 mg·kg- 1·d- 1） or high-dose（ 10 mg·kg- 1·d- 1） fluoxetine was applied to inhibit pulmonary arterial hypertension. The hemodynamics,morphology of pulmonary arterioles and lungs,UCH-L1 protein expression and nuclear factor-κB（ NF-κB） nuclear translocation were observed. Results Monocrotaline not only increased pulmonary arterial pressure and promoted pulmonary arterial remodelling and lung inflammation,but also down-regulated UCH-L1 protein expression and increased NF-κB activity in lungs. Fluoxetine inhibited these changes in a dose-dependent manner.However,UCH-L1 protein expression of pulmonary arteries did not significantly change among different groups. Conclusion Fluoxetine inhibits monocrotaline-induced lung inflammation in rats,involved in NF-κB activity inhibited by up-regulated UCH-L1 protein expression.