Fukui T, Noma T, Mizushige K, Aki Y, Kimura S, Abe Y
Department of Pharmacology, Kagawa Medical University, Japan.
Life Sci. 2000 Apr 14;66(21):2043-9. doi: 10.1016/s0024-3205(00)00531-2.
Oxidative stress is involved in the initiation and development of atherosclerosis in diabetes. We tested the hypothesis that oxidative stress is already increased in early stage type II diabetes, and that troglitazone may prevent the increase. Three groups of 20 week old rats were studied: untreated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II diabetes, OLETF rats treated with troglitazone, and control Long-Evans Tokushima Otsuka (LETO) rats. Plasma lipid hydroperoxides (LOOH) concentration, as an indication of lipid peroxidation, and superoxide dismutase (SOD) activity in the thoracic aorta were measured. Plasma LOOH concentration was significantly higher in non-treated OLETF rats compared to LETO rats and treatment with troglitazone completely prevented this increase. SOD activity was significantly decreased in non-treated OLETF rats compared to LETO rats and troglitazone attenuated the diminution of it. These observations demonstrate oxidative stress is already increased in the early stage of type II diabetes and we confirmed troglitazone has the effect of an antioxidant in vivo.
氧化应激参与糖尿病患者动脉粥样硬化的发生与发展。我们检验了以下假设:氧化应激在II型糖尿病早期就已增强,而曲格列酮可能会阻止这种增强。研究了三组20周龄大鼠:未治疗的大冢长- Evans德岛肥胖(OLETF)大鼠,作为II型糖尿病动物模型;用曲格列酮治疗的OLETF大鼠;以及对照的大冢长- Evans德岛(LETO)大鼠。测量了作为脂质过氧化指标的血浆脂质氢过氧化物(LOOH)浓度以及胸主动脉中超氧化物歧化酶(SOD)活性。与LETO大鼠相比,未治疗的OLETF大鼠血浆LOOH浓度显著更高,而曲格列酮治疗完全阻止了这种升高。与LETO大鼠相比,未治疗的OLETF大鼠SOD活性显著降低,而曲格列酮减弱了其降低程度。这些观察结果表明氧化应激在II型糖尿病早期就已增强,并且我们证实曲格列酮在体内具有抗氧化作用。