Moulakakis Konstantinos G, Poulakou Maria V, Dosios Theodosios, Dontas Ismene, Sokolis Dimitrios P, Vlachos Ioannis S, Safioleas Michael C, Papachristodoulou Antonios, Karayannacos Panagiotis E, Perrea Despina N
Laboratory for Experimental Surgery and Surgical Research, School of Medicine, University of Athens, Greece.
In Vivo. 2008 Sep-Oct;22(5):603-8.
Although it has been suggested that the hypometabolic state is associated with a decrease in oxidative stress, literature data are controversial, revealing an individuality of oxidant status in relation to tissue properties and responsiveness. Hypothyroidism has profound direct and indirect actions on the vascular system, inducing characteristic hemodynamic changes while the aorta represents an important determinant of vascular performance. This study aims to examine the oxidant status on the aorta in chronic experimental hypothyroidism.
Chronic hypothyroidism was successfully induced in 20 male Wistar rats by administration of 0.05% 6-n-propyl 2-thiouracil in their drinking water for 8 weeks. Age-matched euthyroid rats were used as controls. Lipid peroxidation in the serum was determined by the end-product malondialdehyde (MDA). Oxidative damage to genomic DNA of aortic tissue and serum was investigated by measuring 8-oxo-dG, one of the base modifications produced in DNA by the reaction of reactive oxygen species. Serum lipids measurement was performed.
A hypothyroid state was confirmed by levels of serum thyroid hormones, lipidemic profile, clinical examination, pathological findings and cardiovascular hemodynamics parameters. Hypothyroidism was associated with a significant increase in lipid peroxidation. (MDA 1.44 +/-0.93 vs 0.64 +/- 0.53 nmol/l, p < 0 .01). Levels of 8-oxo-dG on the aortic ring, expressing the oxidant damage on genomic DNA and in the serum, were observed to be significantly raised in the hypothyroid group compared to controls (8-oxodG(serum) 29.22 +/- 17.78 vs. 17.56 +/- 4.44 ng/ml, p < 0.01; 8-oxo-dG(aorta)11.58 +/- 2.70 vs. 4.09 +/- 1.27 ng/ml, p < 0. 001). A statistical correlation between measurements of 8-oxo-dG in the aorta and serum was found (correlation coefficient = 0.36, p < 0.05). A hyperlipidemic profile in hypothyroid animals was revealed.
Vascular oxidative stress seems to play a pivotal role in the evolution of vascular pathology. Hypothyroidism was associated with increased DNA oxidative damage to the aorta. Hypercholesterolemia and an increase in mean arterial pressure associated with hypothyroidism may have a contributive role in the accumulation of damage in nuclear DNA of the vascular wall. 8-Oxo-dG is one of the mutagenic base modifications produced in DNA. Although clinical studies in other tissues have indicated a direct correlation between in vivo 8-oxo-dG formation and pathological processes, its role on the vascular wall needs further investigation.
尽管有研究表明低代谢状态与氧化应激的降低有关，但文献数据存在争议，显示出氧化状态因组织特性和反应性而异。甲状腺功能减退对血管系统有深远的直接和间接作用，会引发特征性的血流动力学变化，而主动脉是血管功能的重要决定因素。本研究旨在探讨慢性实验性甲状腺功能减退时主动脉的氧化状态。
通过在20只雄性Wistar大鼠的饮用水中给予0.05%的6-正丙基-2-硫氧嘧啶8周，成功诱导出慢性甲状腺功能减退。将年龄匹配的甲状腺功能正常的大鼠作为对照。通过终产物丙二醛（MDA）测定血清中的脂质过氧化。通过测量8-氧代脱氧鸟苷（8-oxo-dG）来研究主动脉组织和血清基因组DNA的氧化损伤，8-氧代脱氧鸟苷是活性氧与DNA反应产生的碱基修饰之一。进行血清脂质测定。
通过血清甲状腺激素水平、血脂谱、临床检查、病理结果和心血管血流动力学参数证实了甲状腺功能减退状态。甲状腺功能减退与脂质过氧化显著增加有关。（MDA 1.44±0.93 vs 0.64±0.53 nmol/l，p<0.01）。与对照组相比，甲状腺功能减退组主动脉环上8-氧代脱氧鸟苷的水平（表示基因组DNA和血清中的氧化损伤）显著升高（8-氧代脱氧鸟苷（血清）29.22±17.78 vs. 17.56±4.44 ng/ml，p<0.01；8-氧代脱氧鸟苷（主动脉）11.58±2.70 vs. 4.09±1.27 ng/ml，p<0.001）。发现主动脉和血清中8-氧代脱氧鸟苷的测量值之间存在统计学相关性（相关系数=0.36，p<0.05）。揭示了甲状腺功能减退动物的高脂血症谱。
血管氧化应激似乎在血管病理演变中起关键作用。甲状腺功能减退与主动脉DNA氧化损伤增加有关。甲状腺功能减退相关的高胆固醇血症和平均动脉压升高可能在血管壁核DNA损伤的积累中起促进作用。8-氧代脱氧鸟苷是DNA中产生的诱变碱基修饰之一。尽管其他组织的临床研究表明体内8-氧代脱氧鸟苷的形成与病理过程之间存在直接相关性，但其在血管壁上的作用仍需进一步研究。
