阿托伐他汀减轻氧化型低密度脂蛋白导致的人微血管内皮细胞活化和损伤

摘要

Aim To investigate the effects of atorvas-tatin ( ATV) on activation and injury of microvascular endothelial cells induced by oxidized low density lipo-protein ( ox-LDL) . Methods Cultured human micro-vascular endothelial cells were pre-incubated with ATV for 24 h prior to exposure of endothelial cells to ox-LDL. After exposure of endothelial cells to ox-LDL, the cell viability was measured by MTT method, LDH in supernatants was determined by enzyme activity as-say kit, ICAM-1 in supernatants was assayed by using ELISA method, phosphorylation of NF-κB p65 was de-tected by western blot analysis, transcriptional activity of NF-κB signal pathway was measured by employing dual-luciferase reporter assay system. Results Hu-man microvascular endothelial cells were activated and injured by ox-LDL. Inhibition of the cell viability, re-lease of LDH, expression of ICAM-1, phosphorylation of NF-κB p65 , and up-regulated transcriptional activity of NF-κB induced by ox-LDL were attenuated by ATV. Conclusion ATV can significantly inhibit the activa-tion and injury of human microvascular endothelial cells induced by ox-LDL, and that may be related to inhibition of phosphorylation and transcriptional activity of NF-κB.%目的研究阿托伐他汀( ATV)对氧化型低密度脂蛋白( ox-LDL)导致人微血管内皮细胞活化和损伤的抑制作用。方法采用ox-LDL激活和损伤人微血管内皮细胞。损伤前加入ATV与内皮细胞孵育。细胞暴露于ox-LDL后,MTT法测定细胞活力,酶活性测定法检测培养上清中乳酸脱氢酶( LDH)活力, ELISA 检测上清中 ICAM-1含量, Western blot检测细胞质内NF-κB p65的磷酸化水平,并采用双萤光素酶报告基因检测系统测定NF-κB的核内转录活性。结果 Ox-LDL能导致人微血管内皮细胞的活化和损伤。 ATV的干预可有效减轻ox-LDL对细胞活力的抑制、减少LDH释放、下调ICAM-1分子的表达、减弱细胞质内NF-κB p65的磷酸化、抑制NF-κB核内转录活性的上调。结论 ATV能有效减轻ox-LDL导致的人微血管内皮细胞活化和损伤,其机制可能与抑制NF-κB的磷酸化和核内转录活性有关。