Aguilar Simón A, Arias Pamela V, Canquil Ignacio, Ebensperger Germán, Llanos Aníbal J, Reyes Roberto V, González-Candia Alejandro, Herrera Emilio A
Programa de Fisiopatología, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Rev Med Chil. 2019 Mar;147(3):281-288. doi: 10.4067/S0034-98872019000300281.
Living above 2,500 meters in hypobaric conditions induces pulmonary arterial hypertension of the neonate (PAHN), a syndrome whose main features are: pathological remodeling of the pulmonary vessels, abnormal vascular reactivity and increased oxidative stress. Melatonin could have pulmonary antioxidant, anti-remodeling and vasodilating properties for this condition.
To determine the effect of melatonin at the transcript level of prostanoid pathways in the lung of neonatal lambs gestated and born under hypobaric hypoxia.
Vehicle (1.4% of ethanol, n = 6) or melatonin (1 mg * kg1, n = 5) were administered from the postnatal day 4 to 21 to lambs gestated and born at 3,600 meters above sea level. After one week of treatment completion, lung tissue was obtained, the transcript and protein levels of prostanoid synthases and receptors were assessed by RT-PCR and Western Blot.
Melatonin induced the expression of prostacyclin synthase transcript and increased protein expression of the prostacyclin receptor. In addition, the treatment decreased the expression of transcript and protein of cyclooxygenase-2, without changes in the expression of the prostanoid vasoconstrictor (thromboxane) pathway.
Postnatal treatment with melatonin increases the expression of the prostacyclin-vasodilator pathway without changing the vasoconstrictor thromboxane pathway. Further, the decreased COX-2 induced by melatonin could be an index of lesser oxidative stress and inflammation in the lung.
生活在海拔2500米以上的低压环境会诱发新生儿肺动脉高压(PAHN),该综合征的主要特征包括:肺血管的病理重塑、异常的血管反应性和氧化应激增加。褪黑素可能对这种情况具有肺部抗氧化、抗重塑和血管舒张特性。
确定褪黑素对在低压缺氧环境下妊娠并出生的新生羔羊肺中前列腺素途径转录水平的影响。
从出生后第4天至21天,对在海拔3600米处妊娠并出生的羔羊给予赋形剂(1.4%乙醇,n = 6)或褪黑素(1 mg·kg-1,n = 5)。治疗完成一周后,获取肺组织,通过逆转录聚合酶链反应(RT-PCR)和蛋白质免疫印迹法评估前列腺素合成酶和受体的转录水平及蛋白质水平。
褪黑素诱导前列环素合成酶转录物的表达,并增加前列环素受体的蛋白质表达。此外,该治疗降低了环氧合酶-2的转录物和蛋白质表达,而前列腺素血管收缩剂(血栓素)途径的表达没有变化。
出生后用褪黑素治疗可增加前列环素血管舒张途径的表达,而不改变血管收缩剂血栓素途径。此外,褪黑素诱导的环氧合酶-2减少可能是肺中氧化应激和炎症减轻的一个指标。