普罗布考对溶血磷脂酰胆碱致培养人脐静脉内皮细胞损伤的保护作用

Protective Effects of Probucol on the Cultured Human Umbilical Vein Endothelial Cell Injured by Lysophosphatidylcholine

为探讨普罗布考对溶血磷脂酰胆碱致培养人脐静脉内皮细胞损伤的保护作用 ,采用培养的人脐静脉血管内皮细胞 ,观察溶血磷脂酰胆碱对内皮细胞产生和分泌一氧化氮及其合酶、组织型纤溶酶原激活剂、纤溶酶原激活物抑制剂及乳酸脱氢酶活性的影响 ,并观察普罗布考的保护作用。结果发现 ,溶血磷脂酰胆碱明显增加乳酸脱氢酶活性 (4 8.0± 4 .1比 2 8.0± 7.5 ,P <0 .0 5 ) ,增加细胞死亡率 (9.9± 1.2比 6 .3± 0 .9,P <0 .0 5 ) ;同时抑制内皮型一氧化氮合酶 (4 8.0± 4 .3比 6 3.4± 6 .8)及组织型纤溶酶原激活剂活性 (0 .31± 0 .0 5比 0 .4 3± 0 .0 7,P <0 .0 5 ) ,增强纤溶酶原激活物抑制剂的活性 (1.39± 0 .2 1比 0 .97± 0 .11,P <0 .0 5 ) ,具有剂量—依赖效应。预先应用不同剂量的普罗布考 (10～ 5 0mmol L)后 ,该效应明显减弱。以上提示 ,溶血磷脂酰胆碱能直接损伤内皮细胞 ,抑制组织型纤溶酶原激活剂及内皮型一氧化氮合酶活性 ,增强纤溶酶原激活物抑制剂活性 。

Aim To explore the protective effect of probucol on the human umbilical vein endothelial cell (hUVECs) injured by lysophosphatidylcholine. Methods Confluent hUVECs were incubated with Probucol for 24 h and consequently exposed to lysophosphatidylcholine. Lactate dihydrogenase (LDH), plasminogen activator inhibitor 1 (PAI 1)and tissue plasminogen activator(t PA) activity was measured in cell medium and lysate. Endothelial nitric oxide synthase (eNOS) activity and nitric oxide (NO)production were assessed by endothelial nitric oxide synthase and nitric oxide kits. Results Lysophosphatidylcholine enhanced markedly PAI 1, LDH activity and decreased nitric oxide bioavailability via the inhibited eNOS activity (P<0.01). These effects were attenuated by administration of different dose of probucol (10～50 mmol/L). Conclusions Lysophosphatidylcholine could injure hUVECs and inhibit eNOS and t PA activity directly. Probucol might play a protective role in hUVECs injured by lysophosphatidylcholine.