Singhania N, Puri D, Madhu S V, Sharma S B
Department of Biochemistry, University College of Medical Sciences, Shahdara, Delhi, India.
QJM. 2008 Jun;101(6):449-55. doi: 10.1093/qjmed/hcn020. Epub 2008 Apr 1.
Enhanced oxidative stress coupled with increased expression of adhesion molecules (e.g. VCAM-1, ICAM-1) and decreased nitric oxide (NO) levels are implicated in development of atheromatous vascular lesion in diabetes. The present study addresses the correlation between oxidative stress, vascular cell adhesion molecules-1 (VCAM-1), NO end products and macroangiopathic complications in type 2 diabetes mellitus (DM).
The study population consisted of three groups (i) diabetic patients with macroangiopathy (Group I); (ii) diabetic patients without macroangiopathy (Group II) and (iii) healthy controls (Group III) (n = 30, each group).
Serum malondialdehyde(MDA) concentration was significantly higher in diabetic patients as compared to controls. Group I had significantly higher malondialdehyde level as compared to Group II (P < 0.05) (5.12 +/- 1.83 micromol/l vs. 4.22 +/- 1.03 micromol/l), suggesting higher oxidative stress in patients with macroangiopathy. Significant reduction in NO end products was observed in diabetic patients compared to controls. Levels of serum NO end products levels were further reduced in patients with macroangiopathy compared to those without macroangiopathy. Group I (971.67 +/- 230.13 ng/ml) and Group II (823.55 +/- 197.74 ng/ml) had significantly higher level of sVCAM-1 compared to healthy controls (541.14 +/- 118.25 ng/ml) (P < 0.001). Also, patients with macroangiopathy had significantly higher levels of sVCAM-1 compared to those without macroangiopathy (P < 0.05). Multiple regression analysis indicated that post-prandial blood glucose, GSH and MDA were independent predictors of sVCAM-1 level (R = 0.690, P = 0.000).
It can be concluded from the present study that an enhanced oxidative stress coupled with endothelial dysfunction as indicated by reduced activity of NO pathway and enhanced expression of sVCAM-1 play an important intermediary role in the pathogenesis of macrovascular complications in type 2 DM.
氧化应激增强，再加上黏附分子（如血管细胞黏附分子 -1、细胞间黏附分子 -1）表达增加以及一氧化氮（NO）水平降低，与糖尿病动脉粥样硬化性血管病变的发生有关。本研究探讨了 2 型糖尿病（DM）中氧化应激、血管细胞黏附分子 -1（VCAM -1）、NO 终产物与大血管并发症之间的相关性。
研究人群分为三组：（i）患有大血管病变的糖尿病患者（第一组）；（ii）无大血管病变的糖尿病患者（第二组）；（iii）健康对照者（第三组）（每组 n = 30）。
与对照组相比，糖尿病患者血清丙二醛（MDA）浓度显著更高。与第二组相比，第一组的丙二醛水平显著更高（P < 0.05）（5.12 ± 1.83 μmol/l 对 4.22 ± 1.03 μmol/l），表明大血管病变患者的氧化应激更高。与对照组相比，糖尿病患者的 NO 终产物显著减少。与无大血管病变的患者相比，大血管病变患者的血清 NO 终产物水平进一步降低。与健康对照组（541.14 ± 118.25 ng/ml）相比，第一组（971.67 ± 230.13 ng/ml）和第二组（823.55 ± 197.74 ng/ml）的可溶性血管细胞黏附分子 -1（sVCAM -1）水平显著更高（P < 0.001）。此外，与无大血管病变的患者相比，大血管病变患者的 sVCAM -1 水平显著更高（P < 0.05）。多元回归分析表明，餐后血糖、谷胱甘肽（GSH）和 MDA 是 sVCAM -1 水平的独立预测因素（R = 0.690，P = 0.000）。
从本研究可以得出结论，氧化应激增强以及 NO 途径活性降低和 sVCAM -1 表达增强所表明的内皮功能障碍，在 2 型糖尿病大血管并发症的发病机制中起重要的中介作用。
