A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.

高同型半胱氨酸血症与心血管疾病之间存在联系，尽管其潜在机制仍不完全明确。一种可能性涉及高半胱氨酸（Hcy）诱导的氧化应激增加。褪黑激素（Mel）和维生素E（vitE）是重要的抗氧化剂。这项研究的主要目的是（1）比较Mel，vitE或两者联合治疗对Hcy诱导的人脐静脉内皮细胞（HUVEC）凋亡的影响，以及（2）研究其潜在机制。细胞增殖测定通过水溶性四唑-1（WST-1）测定试剂盒进行。通过TUNEL测定法计算凋亡指数。通过测量活性氧（ROS）和脂质过氧化（LPO）的水平来研究抗氧化参数。分别通过定量实时聚合酶链反应（qRT-PCR）和蛋白质印迹实验研究了凋亡和抗凋亡基因和蛋白质的mRNA和蛋白质表达水平。结果表明，用Mel，vitE或Mel + vitE处理可抑制Hcy诱导的细胞死亡，对于Mel和Mel + vitE处理具有更高的效率。我们的结果表明，这些抗氧化剂保护内皮细胞的机制包括ROS和LPO水平的降低，细胞迁移的增加，促凋亡蛋白Cas 3，Cas 9，Cyt C和Bax的下调以及上调。总的来说，这些结果揭示了vitE和Mel对Hcy诱导的细胞凋亡的保护作用，这可能增加了对Hcy诱导的损伤的治疗方法的认识。