Department of Physiology, Medical School, University Complutense of Madrid, Madrid, Spain.
J Pineal Res. 2010 Oct;49(3):312-20. doi: 10.1111/j.1600-079X.2010.00800.x. Epub 2010 Aug 3.
This study investigated the effect of aging-related parameters such as inflammation, oxidative stress and cell death in the heart in an animal model of accelerated senescence and analyzed the effects of chronic administration of melatonin on these markers. Thirty male mice of senescence-accelerated prone (SAMP8) and 30 senescence-accelerated-resistant mice (SAMR1) at 2 and 10 months of age were used. Animals were divided into eight experimental groups, four from each strain: two young control groups, two old untreated control groups, and four melatonin-treated groups. Melatonin was provided at two different dosages (1 and 10 mg/kg/day) in the drinking water. After 30 days of treatment, the expression of inflammatory mediators (tumor necrosis factor-alpha, interleukin 1 and 10, NFkBp50 and NFkBp52), apoptosis markers (BAD, BAX and Bcl2) and parameters related to oxidative stress (heme oxygenases 1 and 2, endothelial and inducible nitric oxide synthases) were determined in the heart by real-time reverse transcription polymerase chain reaction (RT-PCR). Inflammation, as well as, oxidative stress and apoptosis markers was increased in old SAMP8 males, when compared to its young controls. SAMR1 mice showed significantly lower basal levels of the measured parameters and smaller increases with age or no increases at all. After treatment with melatonin, these age-altered parameters were partially reversed, especially in SAMP8 mice. The results suggest that oxidative stress and inflammation increase with aging and that chronic treatment with melatonin, a potent antioxidant, reduces these parameters. The effects were more marked in the SAMP8 animals.
本研究调查了炎症、氧化应激和细胞死亡等与衰老相关的参数对加速衰老动物模型中心脏的影响，并分析了慢性给予褪黑素对这些标志物的影响。使用了 30 只雄性衰老加速敏感（SAMP8）和 30 只衰老加速抗性（SAMR1）小鼠，它们的年龄分别为 2 个月和 10 个月。动物分为 8 个实验组，每组 30 只，每组均来自两种品系：两个年轻对照组、两个年老未处理对照组，以及四个褪黑素处理组。褪黑素通过饮用水提供两种不同剂量（1 和 10 mg/kg/天）。治疗 30 天后，通过实时逆转录聚合酶链反应（RT-PCR）测定心脏中炎症介质（肿瘤坏死因子-α、白细胞介素 1 和 10、NFkBp50 和 NFkBp52）、凋亡标志物（BAD、BAX 和 Bcl2）和氧化应激相关参数（血红素加氧酶 1 和 2、内皮和诱导型一氧化氮合酶）的表达。与年轻对照组相比，年老的 SAMP8 雄性动物的炎症以及氧化应激和凋亡标志物增加。SAMR1 小鼠表现出显著较低的基础测量参数水平，并且随年龄增长的变化较小或根本没有变化。用褪黑素治疗后，这些随年龄变化的参数部分得到逆转，尤其是在 SAMP8 小鼠中。结果表明，氧化应激和炎症随年龄增长而增加，而慢性给予褪黑素这种有效的抗氧化剂可降低这些参数。在 SAMP8 动物中，效果更为显著。
