Abstract：
Diabetes mellitus is a metabolic disorder caused by a dysfunction in insulin action or secretion, leading to an elevation in blood glucose levels. It is a highly prevalent condition and as a result, the NHS spends 10 % of its entire budget on diabetes mellitus care, that is equivalent to £10 billion a year. Diabetes mellitus has been linked with vascular and neurological complications which may be associated with the progression of neurodegeneration and Alzheimer\'s disease. Chronic hyperglycaemia increases the production of the reactive oxidant species (ROS) such as methylglyoxal (MGO). MGO has been linked with vascular complications, neuropathy and cytotoxicity. The main aim of this study was to investigate the potential beneficial effect of antidiabetic agents such as metformin and dapagliflozin on human brain neuronal cells (SH-SY5Y) treated with MGO. SH-SY5Y cells were cultured in DMEM/F12 media and subjected overnight incubation with one of the following treatment conditions: Control (untreated); MGO (1 μM); MGO (100 μM); metformin (100 μM) + MGO (100 μM); and dapagliflozin (10 μM) + MGO (100 μM). Several assays were conducted to explore the effect of the treatment groups on the SH-SY5Y cells. These included: MTT assay; LDH assay, peroxynitrite fluorescence assay, and laser scanning confocal microscopy. MGO (100 μM) led to significant cell injury and damage and significantly reduced the survival of the cells by approximately 50-75 %, associated with significant increase in peroxynitrite. The addition of metformin (100 μM) or dapagliflozin (10 μM) represented significant protective effects on the cells and prevented the cell damage caused by the high MGO concentration. As a result, the findings of this research reveal that MGO-induced cell damage may partly be mediated by the generation of peroxynitrite, while the antidiabetic agents such as metformin and dapagliflozin prevent brain cell death, which potentially may play prophylactic roles against the risk of dementia in diabetic patients.
摘要：
糖尿病是由胰岛素作用或分泌功能障碍引起的代谢紊乱，导致血糖水平升高。这是一种非常普遍的情况，因此，NHS将其全部预算的10%用于糖尿病护理，这相当于每年100亿英镑。糖尿病与血管和神经并发症有关，这些并发症可能与神经变性和阿尔茨海默病的进展有关。慢性高血糖会增加反应性氧化剂（ROS）的产生，例如甲基乙二醛（MGO）。MGO与血管并发症有关,神经病变和细胞毒性。这项研究的主要目的是研究二甲双胍和达格列净等抗糖尿病药物对MGO治疗的人脑神经元细胞（SH-SY5Y）的潜在有益作用。在DMEM/F12培养基中培养SH-SY5Y细胞,并用以下处理条件之一进行过夜孵育:对照(未处理);MGO(1μM);MGO(100μM);二甲双胍(100μM)+MGO(100μM);和达格列净(10μM)+MGO(100μM)。进行若干测定以探索处理组对SH-SY5Y细胞的作用。其中包括：MTT测定；LDH测定，过氧亚硝酸盐荧光分析，和激光扫描共聚焦显微镜。MGO（100μM）导致明显的细胞损伤和损伤，并使细胞的存活率显着降低约50-75％，与过氧亚硝酸盐的显着增加有关。添加二甲双胍（100μM）或达格列净（10μM）对细胞具有显着的保护作用，并防止了由高MGO浓度引起的细胞损伤。因此,这项研究的结果表明，MGO诱导的细胞损伤可能部分是由过氧亚硝酸盐的产生介导的，虽然抗糖尿病药物如二甲双胍和达格列净可预防脑细胞死亡，这可能对糖尿病患者的痴呆风险起到预防作用。
