Zhang Jing, Slevin Mark, Duraisamy Yasotha, Gaffney John, A Smith Christopher, Ahmed Nessar
School of Biology, Chemistry and Health Science, Manchester Metropolitan University, Oxford Road, Manchester M1 5GD, UK.
Biochim Biophys Acta. 2006 May;1762(5):551-7. doi: 10.1016/j.bbadis.2006.02.004. Epub 2006 Mar 20.
This study compared the protective effects of three different anti-glycation compounds, aspirin, D-penicillamine and vitamin E, against high glucose and advanced glycation endproduct (AGE) mediated toxicity in cultured bovine aortic endothelial cells using two approaches. Their proliferation was assessed in culture in different concentrations of glucose (5.5-100 mmol/l) with and without these inhibitors. A monolayer of cultured endothelial cells was wounded and recovery at the wound site was measured following exposure to different concentrations of glucose with and without inhibitors. The ability of these compounds to protect cultured endothelial cells following exposure to bovine serum albumin-derived advanced glycation endproducts (BSA-AGE) was also studied. Addition of glucose to cultured endothelial cells inhibited their proliferation in a dose dependent manner. All three compounds protected against the anti-proliferative effects of high glucose, with vitamin E being the most effective. The migration of cultured endothelial cells following wounding was inhibited by increasing concentrations of glucose but was maintained in the presence of all three anti-glycation compounds with vitamin E, again giving the greatest protection. Vitamin E was also the most effective at protecting against the anti-proliferative effects of BSA-AGE. D-penicillamine was not as effective as vitamin E whereas aspirin offered no significant protection against AGE-induced cellular toxicity. Our studies suggest that compounds, such as vitamin E, with combined antiglycation and antioxidant properties offer maximum therapeutic potential in protection against high glucose and AGE-mediated cellular toxicity.
本研究采用两种方法比较了三种不同的抗糖基化化合物——阿司匹林、D-青霉胺和维生素E，对培养的牛主动脉内皮细胞中高糖和晚期糖基化终产物（AGE）介导的毒性的保护作用。在有和没有这些抑制剂的情况下，评估它们在不同浓度葡萄糖（5.5 - 100 mmol/L）培养条件下的增殖情况。对单层培养的内皮细胞进行划痕损伤，然后在有和没有抑制剂的情况下，测量暴露于不同浓度葡萄糖后伤口部位的恢复情况。还研究了这些化合物在暴露于牛血清白蛋白衍生的晚期糖基化终产物（BSA-AGE）后对培养的内皮细胞的保护能力。向培养的内皮细胞中添加葡萄糖会以剂量依赖的方式抑制其增殖。所有三种化合物都能对抗高糖的抗增殖作用，其中维生素E最为有效。随着葡萄糖浓度的增加，培养的内皮细胞损伤后的迁移受到抑制，但在所有三种抗糖基化化合物存在的情况下，迁移得以维持，维生素E再次提供了最大程度的保护。维生素E在对抗BSA-AGE的抗增殖作用方面也是最有效的。D-青霉胺不如维生素E有效，而阿司匹林对AGE诱导的细胞毒性没有显著的保护作用。我们的研究表明，具有抗糖基化和抗氧化特性的化合物，如维生素E，在预防高糖和AGE介导的细胞毒性方面具有最大的治疗潜力。
