Guangdong Provincial Key Laboratory of Food, Nutrition, and Health, School of Public Health, Sun Yat-sen University (Northern Campus), Guangzhou, Guangdong Province, China.
J Nutr. 2013 Aug;143(8):1248-53. doi: 10.3945/jn.113.177451. Epub 2013 Jun 12.
Atherosclerosis is accelerated in diabetes mellitus mainly due to the reduced availability and function of endothelial progenitor cells (EPCs). The purpose of this study was to determine the protective effects of the anthocyanin cyanidin-3-O-β-glucoside (C3G) on EPC function and endothelial repair in diabetic apolipoprotein E-deficient (apoE(-/-)) mice. Diabetes mellitus was induced in 8-wk-old male apoE(-/-) mice with streptozotocin. Diabetic apoE(-/-) mice were fed the AIN-93 diet or an AIN-93 diet supplemented with C3G (0.2% wt:wt) for 6 wk. Sham-injected apoE(-/-) mice fed the AIN-93 diet served as nondiabetic controls. The endothelium-dependent relaxation response to acetylcholine in the aortas of C3G-fed mice was greater by 51% compared with diabetic mice fed the AIN-93 diet (P < 0.05) and was similar to that in nondiabetic apoE(-/-) mice. The capacity of in vitro adhesion to fibronectin, migration, and tube formation was significantly impaired in diabetic EPCs (decreased by 83, 61.9, and 74.5%, respectively, compared with nondiabetic controls; all P < 0.01), which was significantly rescued in response to C3G (increased by 3.9-, 2-, and 1.8-fold compared with diabetic EPCs, respectively; all P < 0.05). At the molecular level, the phosphorylation levels of AMP-activated protein kinase (AMPK) Thr 172 and endothelial nitric oxide synthase (eNOS) Ser1177 were higher in EPCs derived from the C3G-treated diabetic mice compared with those in nondiabetic mice. Furthermore, compared with nondiabetic controls, diabetic apoE(-/-) mice had a 3.5-fold increase in the aortic lesion area, which was lowered by 45% in C3G-fed diabetic mice. This study extends our current knowledge that C3G improves the impairment of EPC function, enhances endothelial repair, and thus limits accelerated atherogenesis caused by diabetes. Our findings emphasize the potential utility of anthocyanin in the prevention and treatment of diabetic vascular complications.
动脉粥样硬化在糖尿病中加速发展，主要是由于内皮祖细胞 (EPC) 的可用性和功能降低。本研究旨在确定花色苷矢车菊素-3-O-β-葡萄糖苷 (C3G) 对糖尿病载脂蛋白 E 缺陷 (apoE(-/-)) 小鼠 EPC 功能和内皮修复的保护作用。用链脲佐菌素诱导 8 周龄雄性 apoE(-/-) 小鼠发生糖尿病。糖尿病 apoE(-/-) 小鼠用 AIN-93 饮食或补充 C3G(0.2%wt:wt)的 AIN-93 饮食喂养 6 周。用 AIN-93 饮食喂养的假注射 apoE(-/-) 小鼠作为非糖尿病对照。与用 AIN-93 饮食喂养的糖尿病小鼠相比，C3G 喂养的小鼠主动脉对乙酰胆碱的内皮依赖性舒张反应增加了 51%(P<0.05)，与非糖尿病 apoE(-/-) 小鼠相似。体外黏附纤维连接蛋白、迁移和管状形成的能力在糖尿病 EPC 中显著受损(分别比非糖尿病对照组降低 83%、61.9%和 74.5%；所有 P<0.01)，而 C3G 则显著恢复(分别比糖尿病 EPC 增加 3.9 倍、2 倍和 1.8 倍；所有 P<0.05)。在分子水平上，C3G 处理的糖尿病 EPC 中 AMP 激活蛋白激酶 (AMPK) Thr 172 和内皮型一氧化氮合酶 (eNOS) Ser1177 的磷酸化水平高于非糖尿病小鼠。此外，与非糖尿病对照组相比，糖尿病 apoE(-/-) 小鼠的主动脉病变面积增加了 3.5 倍，而 C3G 喂养的糖尿病小鼠的病变面积降低了 45%。本研究扩展了我们目前的知识，即 C3G 可改善 EPC 功能障碍，增强内皮修复，从而限制糖尿病引起的动脉粥样硬化加速形成。我们的研究结果强调了花色苷在预防和治疗糖尿病血管并发症方面的潜在应用。
