Endothelial dysfunction, macrophage infiltration and NADPH oxidase-dependent superoxide production were attenuated by erythropoietin in streptozotocin-induced diabetic rat aorta.
Endothelial dysfunction, macrophage infiltration and NADPH oxidase-dependent superoxide production were attenuated by erythropoietin in streptozotocin-induced diabetic rat aorta.
复制标题
在链脲佐菌素诱导的糖尿病大鼠主动脉中，促红细胞生成素可减弱内皮功能障碍、巨噬细胞浸润和 NADPH 氧化酶依赖性超氧化物的产生。
作者：
Wang J;Toba H;Morita Y;Nakashima K;Noda K;Tian W;Kobara M;Nakata T
促红细胞生成素（EPO）已用于治疗肾性贫血。最近的研究表明 EPO 在脑、肾和脉管系统等多种组织中具有多效性。糖尿病是发生血管损伤的主要风险。本研究的目的是调查 EPO 有助于抑制糖尿病大血管病变的假设。将重组人 EPO（rHuEPO；150 U/kg，每周 3 次，皮下注射）给予链脲佐菌素诱导的糖尿病大鼠 4 周。链脲佐菌素（65 mg/kg，静脉注射）显着增加主动脉中巨噬细胞浸润和粘附分子、单核细胞趋化蛋白-1 和骨桥蛋白 mRNA 水平。 rHuEPO 抑制了这些炎症变化。糖尿病大鼠主动脉环中乙酰胆碱的血管舒张功能受损，但 rHuEPO 可以改善血管舒张功能。 rHuEPO 抑制糖尿病大鼠主动脉烟酰胺腺嘌呤二核苷酸磷酸 (NADPH) 氧化酶 mRNA 的表达和 NADPH 氧化酶依赖性超氧化物的产生以及血浆丙二醛浓度的增加。 rHuEPO 还降低了主动脉中晚期糖基化终产物受体的水平。我们还发现 rHuEPO 治疗组的磷酸 Akt 和内皮一氧化氮合酶表达增加，血浆 NOx 水平增加。另一方面，rHuEPO 并不影响糖尿病大鼠的血糖水平、糖化血红蛋白、血压或血细胞比容。这些结果表明 rHuEPO 在糖尿病大鼠主动脉中发挥多效抗氧化和抗炎特性。
Erythropoietin (EPO) has been used for the management of renal anemia. Recent studies suggest the pleiotropic properties of EPO in various tissues such as brain, kidney and vasculature. Diabetes mellitus is a major risk for development of vascular impairment. The aim of the present study was to investigate the hypothesis that EPO would be beneficial in inhibiting diabetic macroangiopathy. Recombinant human EPO (rHuEPO; 150 U/kg, 3 times/week, s.c.) was administered to streptozotocin-induced diabetic rats for 4 weeks. Streptozotocin (65 mg/kg, i.v.) significantly increased macrophage infiltration and adhesion molecules, monocyte chemoattractant protein-1 and osteopontin mRNA levels in the aorta. These inflammatory changes were suppressed by rHuEPO. Vasodilation in response to acetylcholine in the aortic ring was impaired in the diabetic rats, and improved by rHuEPO. rHuEPO inhibited the aortic expression of mRNA for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and the NADPH oxidase-dependent superoxide production and the increase in plasma malondialdehyde concentration in diabetic rats. rHuEPO also decreased the level of the receptor for advanced glycation end products in the aorta. We also found an increased expression of phospho-Akt and endothelial nitric oxide synthase and plasma NOx level in the rHuEPO-treated group. On the other hand, rHuEPO did not affect blood glucose levels, hemoglobin A1c, blood pressure or hematocrit in diabetic rats. These results indicate that rHuEPO exerts pleiotropic antioxidant and anti-inflammatory properties in diabetic rat aorta.