Glimepiride exhibits prophylactic effect on atherosclerosis in cholesterol-fed rabbits
Glimepiride exhibits prophylactic effect on atherosclerosis in cholesterol-fed rabbits
复制标题
DOI：
10.1016/j.atherosclerosis.2005.01.044
复制
发表时间：
2005-10-01
期刊：
影响因子：
5.3
通讯作者：
Tsuchiya, E
中科院分区：
文献类型：
--
作者：
Shakuto, S;Oshima, K;Tsuchiya, E
目的/假设：本研究的目的是探讨格列美脲对家兔实验性动脉粥样硬化的潜在预防作用，并阐明其作用机制。方法：给家兔喂含1%胆固醇和格列美脲0.1 mg/kg/d的致动脉粥样硬化饲料，连续10周。每2周测定一次血脂水平。计算胸主动脉油红0染色的致动脉粥样硬化病变百分比，并对病变进行组织学检查。同时测定胸主动脉和肝脏脂质和脂质过氧化物含量。此外，格列美脲对人冠状动脉内皮细胞介导的LDL oxidations.Results的抑制作用：在油红O阳性动脉粥样硬化病变的动脉内膜的焦点区域的脂质载泡沫细胞的积累进行了评价。格列美脲治疗可显着减少动脉粥样硬化病变（对照组，57.5 +/- 7.1%，而格列美脲，20.6 +/- 4.8%; P < 0.01），血浆脂质水平未观察到显着变化。在接受格列美脲治疗的家兔中，胸主动脉中的脂质和过氧化脂质含量显著降低，而肝脏脂质水平无显著变化。在培养的人冠状动脉内皮细胞中，格列美脲以剂量依赖性方式（IC 50 = 8.8 × 10（-7）M）抑制LDL的氧化修饰，而无细胞毒性。结论/解释：这些发现表明格列美脲可预防脂肪喂养家兔的主动脉粥样硬化的发展。其潜在机制可能是抑制内皮细胞介导的LDL氧化。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Aims/hypothesis: The purpose of this study was to examine the potential prophylactic effect of glimepiride on experimental atherosclerosis in rabbits and to elucidate the mechanism of action.Methods: Rabbits were fed an atherogenic diet containing 1% cholesterol and glimepiride 0.1 mg/kg/day for 10 weeks. Plasma lipid levels were determined every 2 weeks. The percentage of atherogenic lesions of thoracic aorta stained with oil red 0 was calculated and histological examination of the lesions was performed. Lipid and lipid peroxide contents in thoracic aorta and liver were also determined. In addition, the inhibitory effect of glimepiride on human coronary arterial endothelial cell-mediated LDL oxidation was evaluated.Results: Accumulation of lipid-laden foam cells in the focal areas of arterial intima was observed in oil red O-positive atherosclerotic lesions. Glimepiride treatment produced significant reduction of atherosclerotic lesions (control, 57.5 +/- 7.1% versus glimepiride, 20.6 +/- 4.8%; P < 0.01) with no significant change observed in levels of plasma lipids. There were marked decreases in lipid and lipid peroxide contents in the thoracic aorta in glimepiride-treated rabbits with no significant change in levels of liver lipids. In cultured human coronary arterial endothelial cells, glimepiride inhibited oxidative modification of LDL in a dose-dependent manner (IC50 = 8.8 x 10(-7) M) without cytotoxicity.Conclusions/interpretation: These findings suggest that glimepiride prevents the development of aortic atherosclerosis in fat-fed rabbits. The underlying mechanism may be inhibition of endothelial cell-mediated LDL oxidation. (c) 2005 Elsevier Ireland Ltd. All rights reserved.