Yasunari K, Kohno M, Kano H, Yokokawa K, Minami M, Yoshikawa J
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Circulation. 1999 Mar 16;99(10):1370-8. doi: 10.1161/01.cir.99.10.1370.
To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs).
Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C.
These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.
为探讨细胞内氧化应激在高糖诱导动脉粥样硬化形成中的作用，我们研究了普罗布考和/或α-生育酚对培养的兔冠状动脉血管平滑肌细胞（VSMC）迁移和生长特性的影响。
与用正常葡萄糖培养基（5.6 mmol/L + 16.6 mmol/L 甘露糖）处理的VSMC相比，慢性高糖培养基（22.2 mmol/L）处理增加了血小板衍生生长因子（PDGF）-BB介导的VSMC迁移、[3H]胸腺嘧啶核苷掺入及细胞数量。普罗布考和α-生育酚显著抑制高糖诱导的VSMC迁移、细胞数量及[3H]胸腺嘧啶核苷掺入的增加。普罗布考和α-生育酚抑制高糖诱导的胞质NADH/NAD+比率、磷脂酶D及膜结合蛋白激酶C活化的升高。普罗布考、α-生育酚及钙泊三醇改善了高糖诱导的胰岛素介导的[3H]脱氧葡萄糖摄取的抑制。慢性高糖处理增加了氧化应激，普罗布考、α-生育酚、苏拉明及钙泊三醇可显著抑制之。
这些发现提示，普罗布考和α-生育酚可能通过抑制高糖诱导的胞质游离NADH/NAD+比率、磷脂酶D及蛋白激酶C活化的增加来抑制高糖诱导的VSMC迁移和增殖，这些变化导致细胞内氧化应激降低。
