摘要
目的探讨洛伐他汀(Lov)对溶血性磷脂酰胆碱(LPC)所致血管内皮损伤的保护作用及机制。方法利用家兔离体胸主动脉环和培养的人内皮细胞模型,分别观察洛伐他汀对LPC致离体血管环内皮依赖性舒张反应的损伤及对内皮细胞合成NO的损伤的保护作用。血管环分别与LPC(4 mg.L-1)和洛伐他汀(0.025、0.05、0.1μmol.L-1)单独孵育和共孵各15 min,分别检测乙酰胆碱(ACh)诱导的内皮依赖性舒张(EDR)反应及硝普钠诱导的非内皮依赖性舒张(EDR)反应及血管组织中的脂质过氧化物产物丙二醛(MDA)的含量。在培养的人内皮细胞和培养基中分别加入LPC和洛伐他汀,分别检测LPC和洛伐他汀对内皮细胞中一氧化氮(NO)含量和一氧化氮合酶(eNOS)的影响。结果LPC(4 mg.L-1)与血管环孵育15 min,引起了血管EDR的显著降低,最大舒张比值较对照组明显减小(P<0.01),洛伐他汀剂量依赖性地减轻了LPC对血管EDR的损伤作用,其最大舒张比值较LPC损伤组明显增加,(P<0.01)。LPC和洛伐他汀对硝普钠诱导的非内皮依赖性舒张反应无明显影响。LPC引起了血管组织中MDA浓度明显升高,与对照组相比有显著性差异(P<0.01);不同浓度的洛伐他汀与血管环预孵后再与LPC孵育,剂量依赖性地减少了LPC所增加的MDA浓度,与LPC损伤组比较有显著差异(P<0.01)。LPC与培养的内皮细胞孵育,导致了内皮细胞NO含量和eNOS活性的降低,不同浓度的洛伐他汀与内皮细胞预孵后再与LPC孵育,剂量依赖性地提高eNOS活性和NO的含量。结论LPC能直接抑制血管的EDR反应,洛伐他汀能剂量依赖性地拮抗LPC对EDR反应的抑制作用。其机制可能与LPC触发脂质过氧化反应,从而抑制血管内皮细胞NO的合成和增加NO的消耗有关,洛伐他汀通过抗氧化而保护血管内皮细胞的功能。
Objective To explore the protective effect and mechanism of lovastatin on damage of vascular endothelium induced by lysophosphatidylcholine (LPC). Methods The models of both isolated rat thoracic aortic rings and cultured human endothelial cells were used. In the experiment of isolated rat thoracic aortic ring, the rings were incubated with LPC(4 mg ·L-1 ) in absence or presence of lovastatin (0. 025, 0. 05, and 0.1μmol ·L-1 ). The vascular endothelial-dependent relaxation (El)R) and the content of malondialdehyde (MDA) in vascular tissues were measured. In cultured human umbilicus vein endothelial cells (HUVECs), the cells were treated with lovastatin in absence or pres- ence of LPC, the content of NO and eNOS activity in endothelial cell cultured medium were measured. Results LPC markedly decreased EDR response and signifieantly increased MDA content in vascular tissues. The incubation of rings with lovastatin (0. 025, 0.05, and 0.1 μmol·L-1 ) significantly improved EDR response injured by LPC and decreased MDA content increased by LPC. Lovastatin also increased NO content and eNOS activity in cultured human endothelial cells. Conclusion LPC could directly inhibit EDR induced by ACh. Lovastatin may concentration-depend- ently protect endothelial cells from being damaged by LPC. The mechanism of tovastatin may be related to antioxidant defenses.
出处
《中南药学》
CAS
2009年第2期94-99,共6页
Central South Pharmacy
关键词
洛伐他汀
溶血磷脂酰胆碱
内皮依赖性舒张
丙二醛
内皮细胞培养
一氧化氮
一氧化氮合酶
lovastatin
lysophosphatidylcholine
endothelium-dependent relaxation
malondialdehylle
cultured human endothelial cells
nitric oxide
nitricoxide synthase