【摘要】 目的考察木樨草素对溶血性磷脂酰胆碱（LPC）所引起的大鼠主动脉内膜依赖性舒张（EDR）紊乱的改善作用,并通过人脐静脉内皮细胞的研究,进一步探讨了其对内膜的化学保护作用和相关机制。方法制备大鼠内膜完整的主动脉环,苯肾上腺素预收缩,给予LPC刺激,观察其对EDR的影响。MTT测定细胞增殖,RT-PCR检测内皮型一氧化氮合酶（eNOS）、诱导型一氧化氮合酶（iNOS）、环氧合酶（COX）-1和COX-2的mRNA的表达,Western blot法检测细胞外信号调节蛋白激酶（ERK）磷酸化改变。结果 LPC刺激使血管对乙酰胆碱所引起的EDR显著下降。木樨草素通过对内膜源性舒张因子和超极化因子的调节表现出对抗LPC的作用,改善乙酰胆碱引起动脉环的EDR,并呈浓度依赖性;ERK的特异性抑制剂PD98059亦表现出相同的作用。LPC低浓度(<20μmol·L^-1)对内皮细胞表现出细胞增殖作用,高浓度则呈细胞毒性作用,而木樨草素对LPC引起的细胞增殖和细胞毒性均表现出有效的对抗作用。木樨草素和PD98059上调LPC抑制的eNOS和COX-1 mRNA表达,同时对LPC所引起的iNOS和COX-2mRNA表达表现出有效的抑制作用。木樨草素亦有效抑制了LPC所引起的ERK1/2磷酸化活化。结论在大鼠离体动脉环上,木樨草素对抗LPC,通过抑制炎症反应而呈现出血管内膜完整性的保护作用,有效改善了受损的血管内膜依赖性舒张的生物活性。木樨草素改善血管内膜功能紊乱对其在防治心血管疾病方面的应用具有一定的积极意义。更多还原

【Abstract】 AIM To investigate the effect of luteolin on lysophosphatidylcholine（LPC） -induced loss of endothelium-dependent relaxation（EDR） in rat aorta and relative chemoprotection towards the endothelium in human umbilical vein endothelial cells（HUVEC）.METHODS The intact aortic ring,prepared from the rat thoracic aorta,was precontracted with phenylephrine,then acetylcholine（ACh） -induced EDR was investigated in the presence of LPC.Cell proliferation was measured with the MTT method and relative gene expression for eNOS,iNOS,COX-1 and COX-2 was assayed with RT-PCR.The phosphorylation of extracellular-signal-regulated protein kinase（ERK1/2） was also investigated by Western blot analysis.RESULTS Luteolin suppressed the inhibition of EDR by LPC.It affected not only endothelium-derived relaxing factor（EDRF） but also endothelium-derived hyperpolarizing factor（EDHF） in a concentration-dependent manner.PD 98059,a selective inhibitor of ERK,demonstrated a similar effect as luteolin.LPC induced cell proliferation at low concentrations(<20μmol·L^-1),but caused cell death at higher concentrations in endothelial cells.Additional treatment of cells by luteolin reduced the effects of LPC on cell survival under proliferation and death.Both luteolin and PD98059 increased the mRNA levels of eNOS and COX-1 that were suppressed by LPC in HUVEC. Conversely,LPC enhanced transcription of iNOS and COX-2 were reduced by both luteolin and PD98059.LPC induced ERK1/2-phosphorylation in endothelial cells and ERK activation was effectively inhibited by treatment with luteolin.CONCLUSION Luteolin restores LPC-induced loss of EDR in rat aorta and promotes endothelial integrity by inhibition of inflammatory response.Luteolin ameliorated LPC-induced endothelial dysfunction and therefore could have application in the prevention or treatment of cardiovascular disease.更多还原