Department of Ophthalmology, College of Medicine, Inje University, Busan, South Korea.
Graefes Arch Clin Exp Ophthalmol. 2011 Mar;249(3):389-97. doi: 10.1007/s00417-010-1496-5. Epub 2010 Sep 7.
Angiogenic factors such as vascular endothelial growth factor (VEGF), erythropoietin, and angiopoietin play important roles in the pathophysiology of diabetic retinopathy. Increased amounts of reactive oxygen species (ROS) are also known to associated with diabetic retinopathy and VEGF expression. This study evaluated the effect of a simvastatin on ROS generation and the changes in various angiogenic factors in the retinas of diabetic rats.
The rats were divided into normal, diabetes mellitus (DM), and simvastatin-treated groups (each group, n = 10). Diabetes was induced by intraperitoneal injection of streptozotocin into 20 Sprague-Dawley rats. After diabetic induction, simvastatin (5mg/kg) was administered orally to ten rats. The expression levels of VEGF, erythropoietin, angiopoietin 1 and 2, and NADPH oxidase were examined in rat retinas by RT-PCR and Western blot. Superoxide formation was examined by dihydroethidium (DHE) staining.
DHE analysis revealed increased superoxide formation in the retinas of the diabetic group, which was decreased in the group treated with simvastatin. Western blot analysis showed that NADPH oxidase levels were decreased in the diabetic group and remained normal in the simvastatin-treated group. Simvastatin treatment blocked hyperglycemia-induced increases in VEGF, angiopoietin 2 and erythropoietin levels, as demonstrated by RT-PCR and Western blot analysis.
Simvastatin treatment led to suppression of superoxide formation and decreased expression of VEGF, angiopoietin 2 and erythropoietin in diabetic rat retinas.
血管内皮生长因子（VEGF）、促红细胞生成素和血管生成素等血管生成因子在糖尿病性视网膜病变的病理生理学中发挥重要作用。已知活性氧（ROS）的含量增加也与糖尿病性视网膜病变和 VEGF 表达有关。本研究评估了辛伐他汀对糖尿病大鼠视网膜 ROS 生成和各种血管生成因子变化的影响。
将大鼠分为正常组、糖尿病组（DM）和辛伐他汀治疗组（每组 10 只）。将链脲佐菌素（STZ）腹膜内注射到 20 只 Sprague-Dawley 大鼠中诱导糖尿病。糖尿病诱导后，10 只大鼠给予辛伐他汀（5mg/kg）口服治疗。通过 RT-PCR 和 Western blot 检测大鼠视网膜中 VEGF、促红细胞生成素、血管生成素 1 和 2 以及 NADPH 氧化酶的表达水平。通过二氢乙啶（DHE）染色检测超氧阴离子的形成。
DHE 分析显示糖尿病组视网膜中超氧阴离子的形成增加，而辛伐他汀治疗组则减少。Western blot 分析显示，糖尿病组 NADPH 氧化酶水平降低，而辛伐他汀治疗组保持正常。辛伐他汀治疗阻断了高血糖诱导的 VEGF、血管生成素 2 和促红细胞生成素水平的升高，这通过 RT-PCR 和 Western blot 分析得到证实。
辛伐他汀治疗导致糖尿病大鼠视网膜中超氧阴离子的形成减少和 VEGF、血管生成素 2 和促红细胞生成素表达降低。
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