Chang K-C, Tseng C-D, Wu M-S, Liang J-T, Tsai M-S, Cho Y-L, Tseng Y-Z
Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Eur J Clin Invest. 2006 Aug;36(8):528-35. doi: 10.1111/j.1365-2362.2006.01672.x.
Formation of advanced glycation end-products (AGEs) on collagen within the arterial wall may be responsible for the development of diabetic vascular injury. This study focused on investigating the role of aminoguanidine (AG), an inhibitor of AGE formation, in the prevention of noninsulin-dependent diabetes mellitus (NIDDM)-derived arterial stiffening and cardiac hypertrophy in rats.
The NIDDM was induced in male Wistar rats, which were administered intraperitoneally with 180 mg kg(-1) nicotinamide (NA) 30 min before an intravenous injection of 50 mg kg(-1) streptozotocin (STZ). After induction of diabetes mellitus type 2, animals receiving daily peritoneal injections with 50 mg kg(-1) AG for 8 weeks were compared with the age-matched, untreated, diabetic controls.
After exposure to AG, the STZ-NA diabetic rats had improved aortic distensibility, as evidenced by 18.8% reduction of aortic characteristic impedance (P < 0.05). Treatment of the experimental syndrome with AG also resulted in a significant increase in wave transit time (+23.7%, P < 0.05) and a decrease in wave reflection factor (-26.6%, P < 0.05), suggesting that AG may prevent the NIDDM-induced augmentation in systolic load of the left ventricle. Also, the glycation-derived modification on aortic collagen was found to be retarded by AG. The diminished ratio of left ventricular weight to body weight suggested that prevention of the diabetes-related cardiac hypertrophy by AG may correspond to the drug-induced decline in aortic stiffening.
Long-term administration of AG to the STZ-NA diabetic rats imparts significant protection against the NIDDM-derived impairment in vascular dynamics, at least partly through inhibition of the AGE accumulation on collagen in the arterial wall.
动脉壁内胶原蛋白上晚期糖基化终产物（AGEs）的形成可能是糖尿病血管损伤发生的原因。本研究聚焦于探讨氨基胍（AG）（一种AGE形成抑制剂）在预防大鼠非胰岛素依赖型糖尿病（NIDDM）所致动脉僵硬和心脏肥大中的作用。
雄性Wistar大鼠被诱导患NIDDM，在静脉注射50mg/kg链脲佐菌素（STZ）前30分钟腹腔注射180mg/kg烟酰胺（NA）。诱导2型糖尿病后，将每日腹腔注射50mg/kg AG持续8周的动物与年龄匹配的未治疗糖尿病对照组进行比较。
暴露于AG后，STZ-NA糖尿病大鼠的主动脉扩张性得到改善，主动脉特征阻抗降低18.8%证明了这一点（P<0.05）。用AG治疗实验综合征还导致波传播时间显著增加（+23.7%，P<0.05）和波反射因子降低（-26.6%，P<0.05），表明AG可能预防NIDDM诱导的左心室收缩负荷增加。此外，发现AG可延缓主动脉胶原蛋白上糖基化衍生的修饰。左心室重量与体重之比降低表明AG预防糖尿病相关心脏肥大可能与药物诱导的主动脉僵硬减轻有关。
对STZ-NA糖尿病大鼠长期给予AG可显著保护其免受NIDDM所致的血管动力学损害，至少部分是通过抑制动脉壁胶原蛋白上AGE的积累实现的。
