Departmentsof Anesthesiology and Molecular Pharmacology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.
Hypertension. 2010 Apr;55(4):998-1004. doi: 10.1161/HYPERTENSIONAHA.110.150623. Epub 2010 Mar 1.
Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper- and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.
先前的研究表明，促红细胞生成素（EPO）的治疗具有血管保护作用。这些作用的确切机制尚不完全清楚。在本研究中，我们假设 EPO 刺激含铜和锌的超氧化物歧化酶（SOD1）的表达和活性，从而保护血管组织免受过量超氧阴离子引起的氧化应激。用 EPO 治疗野生型小鼠 2 周（1000U/kg，SC，每两周一次）可显著增加主动脉 SOD1 的表达。这一作用导致治疗小鼠主动脉中超氧阴离子浓度的显著降低。在 SOD1 缺陷型小鼠中，EPO 降低血管中超氧阴离子产生的能力被消除。在颈动脉普通丝线损伤的小鼠模型中，用 EPO 治疗野生型小鼠可预防病理性重塑，而 SOD1 缺陷型小鼠中则不存在 EPO 的血管作用。我们的发现表明，EPO 治疗可增加血管 SOD1 的表达。这种作用似乎是 EPO 血管保护的重要分子机制。
