Siqueira Rafaela, Colombo Rafael, Conzatti Adriana, de Castro Alexandre Luz, Carraro Cristina Campos, Tavares Angela Maria Vicente, Fernandes Tânia Regina Gattelli, Araujo Alex Sander da Rosa, Belló-Klein Adriane
Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Physiology Department, Institute of Basic Health Science (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Can J Physiol Pharmacol. 2018 Mar;96(3):295-303. doi: 10.1139/cjpp-2016-0445. Epub 2017 Aug 30.
The aim of this study was to evaluate the impact of ovariectomy on oxidative stress in the right ventricle (RV) of female rats with pulmonary arterial hypertension (PAH) induced by monocrotaline (MCT). Rats were divided into 4 groups (n = 6 per group): sham (S), sham + MCT (SM), ovariectomized (O), and ovariectomized + MCT (OM). MCT (60 mg·kg i.p.) was injected 1 week after ovariectomy or sham surgery. Three weeks later, echocardiographic analysis and RV catheterisation were performed. RV morphometric, biochemical, and protein expression analysis through Western blotting were done. MCT promoted a slight increase in pulmonary artery pressure, without differences between the SM and OM groups, but did not induce RV hypertrophy. RV hydrogen peroxide increased in the MCT groups, but SOD, CAT, and GPx activities were also enhanced. Non-classical antioxidant defenses diminished in ovariectomized groups, probably due to a decrease in the nuclear factor Nrf2. Hemoxygenase-1 and thioredoxin-1 protein expression was increased in the OM group compared with SM, being accompanied by an elevation in the estrogen receptor β (ER-β). Hemoxygenase-1 and thioredoxin-1 may be involved in the modulation of oxidative stress in the OM group, and this could be responsible for attenuation of PAH and RV remodeling.
本研究旨在评估卵巢切除术对用野百合碱(MCT)诱导的肺动脉高压(PAH)雌性大鼠右心室(RV)氧化应激的影响。大鼠分为4组(每组n = 6):假手术组(S)、假手术+MCT组(SM)、卵巢切除组(O)和卵巢切除+MCT组(OM)。在卵巢切除术或假手术后1周注射MCT(60 mg·kg腹腔注射)。3周后,进行超声心动图分析和右心室插管。通过蛋白质印迹法进行右心室形态计量学、生化和蛋白质表达分析。MCT使肺动脉压力略有升高,SM组和OM组之间无差异,但未诱导右心室肥大。MCT组右心室过氧化氢增加,但超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)活性也增强。卵巢切除组非经典抗氧化防御减弱,可能是由于核因子Nrf2减少。与SM组相比,OM组血红素加氧酶-1和硫氧还蛋白-1蛋白表达增加,同时雌激素受体β(ER-β)升高。血红素加氧酶-1和硫氧还蛋白-1可能参与OM组氧化应激的调节,这可能是PAH减轻和右心室重塑的原因。