背景:尽管有可用的治疗方法,肺动脉高压(PAH)预后较差。
目的:我们旨在研究alamandine(ALA)的作用,褪黑激素(MEL),和ALA+MEL在PAH中。
方法:大鼠随机分为对照组(n=10),野百合碱(MCT)(n=12),ALA(n=12),MEL(n=12),和ALA+MEL(n=12)组。MCT诱导PAH。ALA,MEL,ALA+MEL组接受50μg/kg/天ALA,10mg/kg/天MEL,ALA+MEL,分别,35天超声心动图和血液动力学测量和组织分析(形态计量学,组织病理学,ELISA,和蛋白质印迹)进行。
结果:单一疗法,尤其是MEL,降低右心室(RV)收缩压。只有MEL增加了肺动脉加速时间。MCT增加了RV/左心室(LV)室间隔(IVS)的比率。而ALA和ALA+MEL略微降低RV/(LV+IVS),MEL大大恢复了它。MCT增加了内膜-中膜(TIM)厚度,肺小动脉PCNA和α-SMA,组织病理学评分(HS)(炎症浸润等。)的肺,和RV。所有处理都降低了TIM厚度(尤其是MEL),PCNA,和α-SMA。所有治疗方法均显着降低了肺部的HS;然而,MEL和ALA+MEL产生更大的益处。所有处理均减弱了RV的HS。MCT引起肺赖氨酰氧化酶(LOX)活性的显著增加。所有治疗都恢复了LOX;然而,MEL和ALA+MEL提供了更大的改进。虽然肺Nrf-2在MCT治疗的大鼠中增加,MEL减少了它。
结论:ALA,MEL,和ALA+MEL减弱PAH并通过抗增殖保护RV,抗重塑,抗肥大,抗炎,和自由基清除能力(仅MEL)。总的来说,MEL产生了最好的结果。
BACKGROUND: Despite the available treatments, pulmonary arterial hypertension (PAH) prognosis is poor.
OBJECTIVE: We aimed to investigate the effects of the
alamandine (ALA), melatonin (MEL), and ALA + MEL in PAH.
METHODS: The rats were randomly divided into Control (n = 10), monocrotaline (MCT) (n = 12), ALA (n = 12), MEL (n = 12), and ALA + MEL (n = 12) groups. PAH was induced by MCT. The ALA, MEL, and ALA + MEL groups received 50 μg/kg/day ALA, 10 mg/kg/day MEL, and ALA + MEL, respectively, for 35 days. Echocardiographic and hemodynamic measurements and tissue analyses (morphometric, histopathological, ELISA, and western blot) were performed.
RESULTS: Monotherapies, especially MEL, reduced the right ventricular (RV) systolic pressure. Only MEL increased the pulmonary artery acceleration time. MCT increased the RV/left ventricle (LV) + interventricular septum (IVS) ratio. While ALA and ALA + MEL slightly decreased the RV/(LV + IVS), MEL significantly restored it. MCT increased the tunica intima-media (TIM) thickness, PCNA and α-SMA of pulmonary arterioles, histopathological score (HS) (inflammatory infiltration etc.) of the lung, and RV. All treatments reduced the TIM thickness (especially MEL), PCNA, and α-SMA. All treatments significantly decreased the HS of the lung; however, MEL and ALA + MEL produced greater benefits. All treatments attenuated the HS of RV. MCT caused a significant increase in lung lysyl oxidase (LOX) activity. All treatments restored the LOX; however, MEL and ALA + MEL provided greater improvement. While lung Nrf-2 was increased in MCT-treated rats, MEL reduced it.
CONCLUSIONS: ALA, MEL, and ALA + MEL attenuate PAH and protect RV via antiproliferative, anti-remodeling, antihypertrophic, anti-inflammatory, and free radical scavenging (only MEL) capabilities. Overall, MEL produced the best outcomes.