Renier G, Desfaits A C, Serri O
CHUM Research Center, Notre-Dame Hospital, Department of Nutrition, University of Montreal, Quebec, Canada.
Metabolism. 2000 Feb;49(2 Suppl 1):17-22. doi: 10.1016/s0026-0495(00)80080-3.
Increasing evidence implicates oxidized low-density lipoprotein (LDL) and advanced glycation end products (AGE) in the atherogenesis associated with diabetes mellitus. In the present study, we examined the in vitro effects of gliclazide on LDL oxidation and monocyte adhesion to endothelial cells induced by oxidized LDL and glycated albumin. To assess the clinical relevance of our in vitro findings, we also measured the effect on monocyte adhesion of gliclazide administration to type 2 diabetic patients. Incubation of human monocytes and endothelial cells with increasing concentrations of gliclazide (0 to 10 microg/mL) and native LDL (100 microg/mL) induced a dose-dependent diminution of cell-mediated LDL oxidation. Pretreatment of endothelial cells with gliclazide (0 to 10 microg/mL) before addition of native LDL (100 microg/mL) or glycated albumin (100 microg/mL) resulted in a dose-dependent diminution of oxidized LDL- and glycated albumin-induced monocyte adhesion to endothelial cells. In type 2 diabetic patients, administration of gliclazide inhibits the increased adhesiveness of monocytes to levels similar to those observed in control subjects. These results indicate that gliclazide is an antioxidant and suggest a beneficial effect of this drug in the prevention of atherosclerosis associated with type 2 diabetes.
越来越多的证据表明，氧化型低密度脂蛋白（LDL）和晚期糖基化终末产物（AGE）与糖尿病相关的动脉粥样硬化形成有关。在本研究中，我们检测了格列齐特对LDL氧化以及氧化LDL和糖化白蛋白诱导的单核细胞与内皮细胞黏附的体外作用。为了评估我们体外研究结果的临床相关性，我们还测定了格列齐特对2型糖尿病患者单核细胞黏附的影响。用浓度递增的格列齐特（0至10微克/毫升）和天然LDL（100微克/毫升）孵育人单核细胞和内皮细胞，可导致细胞介导的LDL氧化呈剂量依赖性降低。在加入天然LDL（100微克/毫升）或糖化白蛋白（100微克/毫升）之前，用格列齐特（0至10微克/毫升）预处理内皮细胞，可导致氧化LDL和糖化白蛋白诱导的单核细胞与内皮细胞黏附呈剂量依赖性降低。在2型糖尿病患者中，给予格列齐特可抑制单核细胞黏附性增加，使其降至与对照组相似的水平。这些结果表明，格列齐特是一种抗氧化剂，并提示该药物在预防2型糖尿病相关动脉粥样硬化方面具有有益作用。
