Kim H H, Yoo S E, Lee W S, Rhim B Y, Hong K W
Department of Pharmacology, College of Medicine, Pusan National University, Pusan, South Korea.
Eur J Pharmacol. 1999 Nov 3;383(3):373-9. doi: 10.1016/s0014-2999(99)00552-x.
This study was carried out to examine the inhibitory effects of SKP-450 (2-[2"(1", 3"-dioxolone)-2-methyl]-4-(2'-oxo-1'-pyrrolidinyl)-6-nitro-2H-1-be nzo pyran), a potassium channel opener, on the proliferation and migration stimulated by oxidized low density lipoprotein (LDL) of cultured smooth muscle cells of Wistar Kyoto rat aorta. SKP-450 (10(-7) and 10(-6) M) as well as probucol (10(-7)-10(-5) M) reduced the production of thiobarbituric acid reactive substances from LDL submitted to CuSO(4) (10 microM). The increased [3H]thymidine incorporation and migration (chemotactic and wound-edge) of the cultured smooth muscle cells in association with increased production of platelet-derived growth factor (PDGF)-BB-like immunoreactivity stimulated by oxidized LDL were significantly reduced by SKP-450 (10(-7)-10(-6) M). Inhibition by SKP-450 of the oxidized LDL-stimulated [3H]thymidine incorporation was antagonized by iberiotoxin (10(-7) M), but not by glibenclamide (10(-6) M), suggestive of mediation of Ca(2+)-activated K(+) channel opening in the action of SKP-450. Taken together, SKP-450 inhibited the proliferation and migration of the smooth muscle cells as well as PDGF production stimulated by oxidized LDL, accompanying with its antiperoxidative action.
本研究旨在检测钾通道开放剂SKP - 450（2 - [2"（1", 3"-二氧戊环）- 2 - 甲基]- 4 -（2'-氧代- 1'-吡咯烷基）- 6 - 硝基- 2H - 1 - 苯并吡喃）对Wistar Kyoto大鼠主动脉培养平滑肌细胞氧化型低密度脂蛋白（LDL）刺激的增殖和迁移的抑制作用。SKP - 450（10^(-7)和10^(-6) M）以及普罗布考（10^(-7) - 10^(-5) M）可减少经CuSO₄（10 μM）处理的LDL中硫代巴比妥酸反应性物质的产生。SKP - 450（10^(-7) - 10^(-6) M）可显著降低与氧化型LDL刺激的血小板衍生生长因子（PDGF）- BB样免疫反应性增加相关的培养平滑肌细胞[³H]胸苷掺入和迁移（趋化性和伤口边缘）的增加。SKP - 450对氧化型LDL刺激的[³H]胸苷掺入的抑制作用可被iberiotoxin（10^(-7) M）拮抗，但不能被格列本脲（10^(-6) M）拮抗，提示SKP - 450的作用是通过Ca²⁺激活的K⁺通道开放介导的。综上所述，SKP - 450抑制平滑肌细胞的增殖和迁移以及氧化型LDL刺激的PDGF产生，并伴有其抗过氧化作用。
