过氧化氢诱导牛主动脉内皮细胞损伤和胞内Ca2+升高及钙拮抗剂的抑制作用

为探讨缺氧/缺血过程中自由基损伤与钙超载的关系,观察了过氧化氢(H₂O₂)诱导培养牛主动脉内皮细胞(BAEC)的损伤和胞内游离钙(Ca²⁺]i)的变化。结果表明,H₂O₂可剂量、时间依赖地诱导BAEC活性下降(MTT值下降),脂质过氧化产物丙二醛(MDA)生成显著增加,同时伴有Ca²⁺]i迅速显著升高。钙拮抗剂硝苯地平可剂量依赖地抑制H₂O₂引起的Ca²⁺]i升高;同时能显著升高BAEC的MTT值,降低MDA生成,有效对抗H₂O₂诱导的BAEC损伤。提示,H₂O₂诱导内皮损伤可能与升高Ca²⁺]i有关,Ca²⁺超载可能是活性氧致损伤的途径之一。钙拮抗剂对活性氧损伤具有一定保护作用。

EFFECTS OF CALCIUM INHIBITOR ON HYDROGEN PEROXIDE-INDUCED DAMAGE AND CALCIUM INFLUX IN BOVINE AORTIC ENDOTHELIAL CELLS IN CULTURE

Hydrogen peroxide(H2O2)-induced cell damage and Ca2+ influx into bovine aortic endothelial cells (BAEC) were investigated. Our data suggested that H2O2 could dose- and time-dependently induce damage in cultured BAEC assessed by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay and increase malondialdehyde (MDA) production, which reflects the level of lipid peroxidation. Exposure of BAEC to H2O2 (100 mumol.L-1) caused significant increase in intracellular free calcium (Ca2+]i) within 6 min, suggesting that the increase of Ca2+]i might implicate in H2O2-induced cell damage. The calcium inhibitor nifedipine was found to dose-dependently decrease the increase of Ca2+]i caused by H2O2 and protect BAEC against H2O2-induced damage reflected by significant decrease of MDA production and increase of MTT value. These results indicate that overload of calcium might be responsible to some extent causing oxidative damage to cells.