Resveratrol Shows Vasoprotective Effect Reducing Oxidative Stress Without Affecting Metabolic Disturbances in Insulin-dependent Diabetes of Rabbits
Resveratrol Shows Vasoprotective Effect Reducing Oxidative Stress Without Affecting Metabolic Disturbances in Insulin-dependent Diabetes of Rabbits
复制标题
DOI：
10.1007/s10557-010-6255-7
复制
发表时间：
2011-04-01
影响因子：
3.4
通讯作者：
Surucu, H. Selcuk
中科院分区：
文献类型：
--
作者：
Akar, Fatma;Pektas, M. Bilgehan;Surucu, H. Selcuk
白藜芦醇已被证明在各种病理生理条件下通过上调氧化防御机制而具有血管保护作用。然而，白藜芦醇对糖尿病氧化应激以及血管和代谢异常的影响尚不完全清楚。因此，本研究旨在评估长期补充白藜芦醇是否对胰岛素依赖型糖尿病患者的血管功能和完整性具有保护作用，并与代谢参数和氧化应激相关。白藜芦醇剂量为5 mg/L(注射前14天开始)和50 mg/L(注射前8或10周，同时或注射前14天开始)。糖尿病动物对乙酰胆碱的松弛受损(对照组75.6+/-3.59%，糖尿病42.23+/-2.53%)，对苯肾上腺素的收缩增加(对照组136.89±2.27%，糖尿病159.37+/-6.27%)。这些变化与基础或NAD(P)H诱导的超氧化物歧化生成增加有关，以及主动脉样本中脂质过氧化和超氧化物歧化酶(SOD)水平的增加。白藜芦醇可使糖尿病兔对乙酰胆碱的最大松弛提高75.74±9.04%。在白藜芦醇治疗后，对苯肾上腺素增加的收缩没有恢复到对照组的值，但对收缩的敏感性有下降的趋势。白藜芦醇增加亚硝酸盐/硝酸盐水平，抑制基础或NAD(P)H诱导的动脉超氧化物歧化和过氧化脂质水平。重要的是，白藜芦醇提高了糖尿病兔的血清胰岛素水平，而不影响血糖和血脂水平。电子显微镜检查发现，白藜芦醇对糖尿病的内皮完整性有明显的保护作用。总体而言，白藜芦醇治疗组在糖尿病恢复方面没有明显差异。我们的结果表明，白藜芦醇通过减少血管氧化应激从而在不改变代谢异常的情况下增加一氧化氮的生物利用度来减轻1型糖尿病引起的血管病变。
Resveratrol has been shown to have vasoprotective effects by upregulating oxidative defense mechanisms in a variety of pathophysiological conditions. However, the effect of resveratrol on diabetic oxidative stress and vascular and metabolic abnormalities is not completely understood. Therefore, this study was designed to evaluate whether long-term resveratrol supplementation has a protective effect on vascular function and integrity in association with metabolic parameters and oxidative stress in insulin-dependent diabetes.Diabetes was induced in rabbits with alloxan and maintained for 8 weeks. We used a resveratrol dose of 5 mg/L (10 weeks, starting 14 days before alloxan injection) and 50 mg/L (8 or 10 weeks, starting concomitantly or 14 days before alloxan injection) in the drinking water of rabbits.Relaxation to acetylcholine was impaired (control 75.6 +/- 3.59%, versus diabetic 42.23 +/- 2.53%) and contractions to phenylephrine increased (control 136.89 +/- 2.27%, versus diabetic 159.37 +/- 6.27%) in aortas from diabetic animals. These changes were associated with increased basal or NAD(P)H-induced superoxide production, as well as lipid peroxide and superoxide dismutase (SOD) levels in the aortic samples. The maximal relaxation to acetylcholine improved by 75.74 +/- 9.04% in diabetic rabbits treated with resveratrol. The increased contractions to phenylephrine were not restored to control values after resveratrol treatments, but sensitivity to the contractions tended to decrease. Resveratrol increased nitrite/nitrate levels and suppressed basal or NAD(P)H-induced superoxide production and lipid peroxide levels in the aortas. Importantly, resveratrol increased serum insulin levels without affecting blood glucose and the lipid profile in diabetic rabbits. Using electron microscopic examinations, resveratrol was found to markedly protect the endothelial integrity from diabetes.Overall, there was no noticeable difference between resveratrol treatment groups on the recovery from diabetes. Our results indicate that resveratrol alleviates type 1 diabetes-induced vasculopathy by decreasing vascular oxidative stress and thereby increasing the bioavailability of nitric oxide without changing metabolic abnormalities.