Vural Pervinl, Kabaca Gulcan, Firat Refia Deniz, Degirmencioglu Sevgin
Department of Biochemistry, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
Department of Oral Surgery, Istanbul Faculty of Dentistry, Istanbul University, Istanbul, Turkey.
Cell J. 2017 Oct;19(3):452-460. doi: 10.22074/cellj.2017.4161. Epub 2017 Aug 19.
The imbalance in oxidant/antioxidant status plays a pivotal role in diabetes mellitus (DM). Selenium is a integral component of the antioxidant enzyme glutathione peroxidase. Se treatment induces angiogenesis and improves endothelial function through increased expression of vascular endothelial growth factor (VEGF). The aim of this study is to investigate the effect of selenium on oxidative stress, VEGF, and endothelin 1 (ET1) in a DM rat model.
We performed an experimental animal study with 64 adult male Wistar-Albino rats. Rats were divided into the following groups (n=8): control (C)7, C21, C+sodium selenite (Se)7, and C+Se21 (control rats), and DM7, DM21, DM+Se7, and DM+Se21 (diabetic rats). Diabetes was induced by 2-deoxy-2-(3-methyl-3-nitrosoureido)- D-glucopyranose [streptozotocin (STZ)]. Three weeks after STZ, DM+Se7 rats received intraperitoneal (i.p.) injections of 0.4 mg/kg Se for 7 days. The DM+Se21 rats received these injections for 21 days. The same dose/duration of Se was administered to the C+Se7 and C+Se21 groups. The remaining rats (C7, C21, DM7, DM21) received physiologic saline injections for 7 or 21 days. Ferric reducing antioxidant power (FRAP), malondialdehyde (MDA), advanced oxidation protein products (AOPP), and endothelial function markers (VEGF and ET1) in plasma samples were measured.
Diabetic rats (DM7 and DM21) had significantly increased plasma FRAP (P=0.002, P=0.001), AOPP (P=0.024, P=0.01), MDA (P=0.004, P=0.001), and ET1 (P=0.028, P=0.003) levels compared with C7 and C21 control rats. VEGF (P=0.02, P=0.01) significantly decreased in DM7 and DM21 diabetic rats compared with their controls (C7, C21). Se administration reversed the increased MDA and decreased VEGF levels, and lowered plasma glucose levels in the DM+Se7 and DM+Se21 diabetic groups compared with diabetic rats (DM7, DM21). We observed positive correlations between FRAP-AOPP (r=0.460), FRAP-ET1 (r=0.510), AOPP-MDA (r=0.270), and AOPP-ET1 (r=0.407), and a negative correlation between MDA-VEGF (r=-0.314).
We observed accentuated oxidative stress and impaired endothelial function in diabetes. Se treatment reduced lipid peroxidation and hyperglycemia. Se probably improved endothelial dysfunction in diabetic rats because of the increased VEGF levels.
氧化/抗氧化状态失衡在糖尿病（DM）中起关键作用。硒是抗氧化酶谷胱甘肽过氧化物酶的重要组成部分。硒治疗可通过增加血管内皮生长因子（VEGF）的表达诱导血管生成并改善内皮功能。本研究旨在探讨硒对糖尿病大鼠模型氧化应激、VEGF和内皮素1（ET1）的影响。
我们对64只成年雄性Wistar - Albino大鼠进行了实验动物研究。大鼠分为以下几组（n = 8）：对照组（C）7天组、C21天组、C + 亚硒酸钠（Se）7天组和C + Se21天组（对照大鼠），以及DM7天组、DM21天组、DM + Se7天组和DM + Se21天组（糖尿病大鼠）。糖尿病通过2 - 脱氧 - 2 -（3 - 甲基 - 3 - 亚硝基脲基）- D - 吡喃葡萄糖[链脲佐菌素（STZ）]诱导。STZ注射3周后，DM + Se7大鼠腹腔内（i.p.）注射0.4 mg/kg硒，共7天。DM + Se21大鼠接受这些注射21天。C + Se7组和C + Se21组给予相同剂量/持续时间的硒。其余大鼠（C7、C21、DM7、DM21）接受7天或21天的生理盐水注射。测量血浆样本中的铁还原抗氧化能力（FRAP）、丙二醛（MDA）、晚期氧化蛋白产物（AOPP）和内皮功能标志物（VEGF和ET1）。
与C7和C21对照大鼠相比，糖尿病大鼠（DM7和DM21）的血浆FRAP（P = 0.002，P = 0.001）、AOPP（P = 0.024，P = 0.01）、MDA（P = 0.004，P = 0.001）和ET1（P = 0.028，P = 0.003）水平显著升高。与对照组（C7、C21）相比，DM7和DM21糖尿病大鼠的VEGF（P = 0.02，P = 0.01）显著降低。与糖尿病大鼠（DM7、DM21）相比，硒给药可逆转DM + Se7和DM + Se21糖尿病组中升高的MDA和降低的VEGF水平，并降低血浆葡萄糖水平。我们观察到FRAP - AOPP（r = 0.460）、FRAP - ET1（r = 0.510）、AOPP - MDA（r = 0.270）和AOPP - ET1（r = 0.407）之间呈正相关，MDA - VEGF（r = - 0.314）之间呈负相关。
我们观察到糖尿病患者氧化应激加剧和内皮功能受损。硒治疗可降低脂质过氧化和高血糖。由于VEGF水平升高，硒可能改善了糖尿病大鼠的内皮功能障碍。
