Programa de Pós-Graduação em Ciência Biológicas: Farmacologia e Terapêutica, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil.
Programa de Pós-Graduação em Ciência Biológicas: Fisiologia, Universidade Federal do Rio Grande do Sul - UFRGS, Porto Alegre, Brazil.
Br J Pharmacol. 2017 Oct;174(19):3302-3314. doi: 10.1111/bph.13948. Epub 2017 Aug 14.
In cor pulmonale, the increased afterload imposed on the right ventricle (RV) generates a maladaptive response, impairing the contractile cardiac function. Oxidative mechanisms play an important role in the pathophysiology and progression of this disease. The administration of pterostilbene (PTS), a phytophenol with antioxidant potential, may represent a therapeutic option. In the present study, we evaluated the effect of PTS complexed with hydroxypropyl-β-cyclodextrin (HPβCD) on hypertrophy, contractile function and oxidative parameters in the RV of rats with pulmonary hypertension, induced by the administration of monocrotaline (MCT).
The rats received daily doses of the PTS : HPβCD complex at 25, 50 or 100 mg·kg , p.o., for 14 days. The diastolic function, E/A ratio, and systolic function, shortening fraction, fractional area change (FAC) and tricuspid annular plane systolic excursion (TAPSE) of the RV were determined by echocardiography.
The PTS : HPβCD complex reduced the production of NADPH oxidase-dependent superoxide anions and oxidative stress in the RV of MCT-treated rats in a dose-dependent manner. At higher doses it prevented the reduction in FAC and TAPSE in MCT-treated animals.
The PTS : HPβCD complex prevented the maladaptative remodelling and protected systolic function in the RV of rats with pulmonary hypertension. These cardioprotective mechanisms may be related, in part, to the antioxidant potential of PTS, favoured by the increased p.o. bioavailability promoted by the presence of HPβCD in the complex.
在肺心病中,右心室(RV)所承受的后负荷增加会导致适应性反应受损,从而损害收缩功能。氧化机制在该疾病的病理生理学和进展中起着重要作用。施用具有抗氧化潜力的植物酚白藜芦醇(PTS)可能是一种治疗选择。在本研究中,我们评估了 PTS 与羟丙基-β-环糊精(HPβCD)复合物对 MCT 诱导的肺动脉高压大鼠 RV 肥大、收缩功能和氧化参数的影响。
大鼠每天口服 PTS:HPβCD 复合物 25、50 或 100mg·kg -1 ,共 14 天。通过超声心动图测定 RV 的舒张功能、E/A 比值、收缩功能、缩短分数、分数面积变化(FAC)和三尖瓣环平面收缩期位移(TAPSE)。
PTS:HPβCD 复合物以剂量依赖性方式降低了 MCT 处理大鼠 RV 中 NADPH 氧化酶依赖性超氧阴离子的产生和氧化应激。在较高剂量下,它可防止 MCT 处理动物 FAC 和 TAPSE 的降低。
PTS:HPβCD 复合物可防止肺动脉高压大鼠 RV 的适应性重塑并保护其收缩功能。这些心脏保护机制可能部分与 PTS 的抗氧化潜力有关,HPβCD 的存在增加了 PTS 的口服生物利用度,从而促进了这种潜力。