Panagiotopoulos S, O'Brien R C, Bucala R, Cooper M E, Jerums G
Department of Medicine, Austin and Repatriation Medical Centre (Austin Campus), University of Melbourne, Heidelberg, Australia.
Atherosclerosis. 1998 Jan;136(1):125-31. doi: 10.1016/s0021-9150(97)00192-5.
Advanced glycosylation endproducts (AGEs) which result from the non-enzymatic interaction of proteins and glucose are implicated in the vasculopathy of diabetes and aging. Since aminoguanidine (A) inhibits the accumulation of AGEs, we explored its effects on the development of atherosclerosis. Male New Zealand white cross rabbits fed a high cholesterol (1%) diet were randomized to control (C) or increasing doses of A treatment (25, 50 and 100 mg/kg A body weight). The animals were sacrificed after 12 weeks. Sudan IV was used to stain the lipid containing plaques of the aortic arch, thoracic and abdominal aorta and the surface area occupied by atheroma was assessed. Increasing doses of A treatment were associated with reduction in plaque formation in the aorta. At a dose of 100 mg/kg A, there was a 30, 49 and 48% reduction in plaque formation in the aortic arch, thoracic and abdominal aorta, respectively. There was a correlation between AGE levels and the degree of atheroma in these cholesterol fed rabbits (control, r = 0.75, P < 0.01; 100 mg/kg A, r = 0.59, P = 0.02). These data suggest that advanced glycation may participate in atherogenesis and raise the possibility that inhibitors of advanced glycation may retard this process.
由蛋白质与葡萄糖的非酶促相互作用产生的晚期糖基化终产物（AGEs）与糖尿病和衰老的血管病变有关。由于氨基胍（A）可抑制AGEs的积累，我们探究了其对动脉粥样硬化发展的影响。将喂食高胆固醇（1%）饮食的雄性新西兰白兔随机分为对照组（C）或给予递增剂量A治疗组（25、50和100mg/kg体重的A）。12周后处死动物。用苏丹IV对主动脉弓、胸主动脉和腹主动脉中含脂质的斑块进行染色，并评估动脉粥样硬化斑块所占的表面积。递增剂量的A治疗与主动脉中斑块形成的减少有关。在100mg/kg A的剂量下，主动脉弓、胸主动脉和腹主动脉中的斑块形成分别减少了30%、49%和48%。在这些喂食胆固醇的兔子中，AGE水平与动脉粥样硬化程度之间存在相关性（对照组，r = 0.75，P < 0.01；100mg/kg A组，r = 0.59，P = 0.02）。这些数据表明晚期糖基化可能参与动脉粥样硬化的发生，并增加了晚期糖基化抑制剂可能延缓这一过程的可能性。
