Role of UCH-L1 in protection of fluoxetine against pulmonary arterial hypertension in rats / 中国药理学通报

ABSTRACT

Aim To study the role of ubiquitin carboxyl terminal hydrolase L1 (UCH-L1)involved in the pro-tective effect of fluoxetine against monocrotaline-in-duced pulmonary arterial hypertension in rats.Meth-ods Monocrotaline (60 mg·kg -1 )was used to es-tablish pulmonary arterial hypertension in rats and low-dose (2 mg·kg -1 ·d -1 )or high-dose (10 mg·kg -1 ·d -1 )fluoxetine was applied to inhibit pulmonary ar-terial hypertension.The hemodynamics,morphology of pulmonary arterioles and lungs,UCH-L1 protein ex-pression and nuclear factor-κB (NF-κB)nuclear trans-location were observed.Results Monocrotaline not only increased pulmonary arterial pressure and promo-ted pulmonary arterial remodelling and lung inflamma-tion,but also down-regulated UCH-L1 protein expres-sion and increased NF-κB activity in lungs.Fluoxetine inhibited these changes in a dose-dependent manner. However,UCH-L1 protein expression of pulmonary ar-teries did not significantly change among different groups.Conclusion Fluoxetine inhibits monocrotal-ine-induced lung inflammation in rats,involved in NF-κB activity inhibited by up-regulated UCH-L1 protein expression.