Puig Ángela, Rancan Lisa, Paredes Sergio D, Carrasco Adrián, Escames Germaine, Vara Elena, Tresguerres Jesús A F
Department of Biochemistry and Molecular Biology III, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain.
Department of Physiology, School of Medicine, Complutense University of Madrid, Avda. Complutense s/n, 28040 Madrid, Spain.
Exp Gerontol. 2016 Mar;75:1-7. doi: 10.1016/j.exger.2015.11.021. Epub 2015 Dec 1.
Aging is associated with an increase in oxidative stress and inflammation. The aging lung is particularly affected since it is continuously exposed to environmental oxidants while antioxidant machinery weakens with age. Melatonin, a free radical scavenger, counteracts inflammation and apoptosis in healthy cells from several tissues. Its effects on the aging lung are, however, not yet fully understood. This study aimed to investigate the effect of chronic administration of melatonin on the expression of inflammation markers (TNF-α, IL-1β, NFκB2, HO-1) and apoptosis parameters (BAD, BAX, AIF) in the lung tissue of male senescence-accelerated prone mice (SAMP8). In addition, RNA oxidative damage, as the formation of 8-hydroxyguanosine (8-OHG), was also evaluated. Young and old animals, aged 2 and 10 months respectively, were divided into 4 groups: untreated young, untreated old, old mice treated with 1mg/kg/day melatonin, and old animals treated with 10mg/kg/day melatonin. Untreated young and old male senescence accelerated resistant mice (SAMR1) were used as controls. After 30 days of treatment, animals were sacrificed. Lungs were collected and immediately frozen in liquid nitrogen. mRNA and protein expressions were measured by RT-PCR and Western blotting, respectively. Levels of 8-OHG were quantified by ELISA. Mean values were analyzed using ANOVA. Old nontreated SAMP8 animals showed increased (p<0.05) mRNA and protein levels of TNF-α, IL-1β, NFκB2, and HO-1 compared to young mice and SAMR1 mice. Melatonin treatment with either dose reversed the aging-derived inflammation (p<0.05). BAD, BAX and AIF expressions also rose with aging, the effect being counteracted with melatonin (p<0.05). Aging also caused a significant elevation (p<0.05) in SAMP8 8-OHG values. This increase was not observed in animals treated with melatonin (p<0.05). In conclusion, melatonin treatment was able to modulate the inflammatory and apoptosis status of the aging lungs, exerting a protective effect on age-induced damage.
衰老与氧化应激和炎症的增加有关。衰老的肺脏受到的影响尤为明显，因为它持续暴露于环境中的氧化剂，而抗氧化机制却随着年龄的增长而减弱。褪黑素作为一种自由基清除剂，可对抗来自多个组织的健康细胞中的炎症和凋亡。然而，其对衰老肺脏的影响尚未完全明确。本研究旨在探讨长期给予褪黑素对雄性快速老化小鼠（SAMP8）肺组织中炎症标志物（TNF-α、IL-1β、NFκB2、HO-1）表达及凋亡参数（BAD、BAX、AIF）的影响。此外，还评估了作为8-羟基鸟苷（8-OHG）形成的RNA氧化损伤情况。分别选取2月龄和10月龄的年轻和老年动物，分为4组：未处理的年轻组、未处理的老年组、用1mg/kg/天褪黑素处理的老年小鼠组以及用10mg/kg/天褪黑素处理的老年动物组。未处理的年轻和老年雄性快速老化抗性小鼠（SAMR1）用作对照。治疗30天后，处死动物。收集肺脏并立即在液氮中冷冻。分别通过RT-PCR和蛋白质印迹法测量mRNA和蛋白质表达。通过ELISA定量8-OHG水平。使用方差分析对平均值进行分析。与年轻小鼠和SAMR1小鼠相比，未处理的老年SAMP8动物的TNF-α、IL-1β、NFκB2和HO-1的mRNA和蛋白质水平升高（p<0.05）。两种剂量的褪黑素治疗均可逆转衰老引起的炎症（p<0.05）。BAD、BAX和AIF的表达也随着衰老而升高，褪黑素可抵消这种作用（p<0.05）。衰老还导致SAMP8的8-OHG值显著升高（p<0.05）。在用褪黑素处理的动物中未观察到这种升高（p<0.05）。总之，褪黑素治疗能够调节衰老肺脏的炎症和凋亡状态，对年龄诱导的损伤发挥保护作用。
