Department of Physiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Br J Pharmacol. 2009 Aug;157(8):1419-26. doi: 10.1111/j.1476-5381.2009.00309.x.
Our team previously demonstrated that diabetes induces a deterioration in vascular dynamics, in parallel with the enhanced formation of advanced glycation end products. The aim of this study was to determine whether prevention of the arterial stiffening by pyridoxamine in diabetes is associated with inhibition of the pathogenic glycation on aortic collagen.
Diabetes was induced in rats by a single tail vein injection with 55 mg.kg(-1) steptozotocin (STZ). After induction of hyperglycaemia, animals were treated for 8 weeks with pyridoxamine (1 g.L(-1) in drinking water) and compared with the age-matched untreated diabetic controls. Pulse wave reflection along the vasculature was derived using the impulse response function of the filtered aortic input impedance spectra.
Treatment of this experimental diabetes with pyridoxamine resulted in a significant increase in wave transit time and a decrease in wave reflection factor, indicating that pyridoxamine attenuates the diabetes-induced augmentation in systolic load of the left ventricle coupled to its arterial system. Meanwhile, pyridoxamine therapy ameliorated the diabetes-related cardiac hypertrophy, as evidenced by the reduction in ratio of the left ventricular weight to body weight. Glycation-derived modification of aortic collagen was also found to be attenuated by administration of pyridoxamine to the STZ-induced diabetic rats.
Pyridoxamine imparts significant protection against the diabetes-induced deterioration in pulsatile arterial load imposed on the heart, at least partly through inhibition of the formation of advanced glycation end products and their accumulation on aortic collagen of the STZ-treated rats.
我们的团队之前已经证明，糖尿病会导致血管动力学恶化，同时也会增强晚期糖基化终产物的形成。本研究的目的是确定在糖尿病中通过吡哆胺预防动脉僵硬是否与抑制主动脉胶原上的致病糖基化有关。
通过单次尾静脉注射 55mg/kg 的链脲佐菌素（STZ）诱导大鼠糖尿病。在诱导高血糖后，动物用吡哆胺（1g/L 在饮用水中）治疗 8 周，并与年龄匹配的未经治疗的糖尿病对照组进行比较。使用滤过的主动脉输入阻抗谱的脉冲响应函数来推导血管中的脉搏波反射。
用吡哆胺治疗这种实验性糖尿病导致脉搏波传导时间显著增加，脉搏波反射因子降低，表明吡哆胺可减轻糖尿病引起的左心室及其动脉系统收缩负荷的增加。同时，吡哆胺治疗还改善了与糖尿病相关的左心室肥大，表现为左心室重量与体重的比值降低。
吡哆胺对 STZ 诱导的糖尿病大鼠的主动脉胶原的糖基化修饰也有明显的抑制作用。吡哆胺对糖尿病引起的心脏搏动性动脉负荷恶化有显著的保护作用，至少部分是通过抑制晚期糖基化终产物的形成及其在 STZ 处理的大鼠主动脉胶原上的积累。
