Arun Mehmet Zuhuri, Üstünes Levent, Sevin Gülnur, Özer Erdener
Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey.
Department of Pathology, School of Medicine, Dokuz Eylül University, Izmir, Turkey.
Drug Des Devel Ther. 2015 Dec 15;9:6461-73. doi: 10.2147/DDDT.S97020. eCollection 2015.
Vitamin C has efficient antioxidant properties and is involved in important physiological processes such as collagen synthesis. As such, vitamin C deficiency leads to serious complications, including vascular diseases. The aim of this study was to investigate the effects of vitamin C treatment on collar-induced intimal thickening. Rabbits were fed a normocholesterolemic diet and a non-occlusive silicon collar was placed around the left carotid artery for 3, 7, and 14 days. The rabbits were treated with or without vitamin C (150 mg/kg/day). Collar-induced intimal thickening became apparent at day 7. The effect of the collar on intimal thickening was more prominent at day 14. Vitamin C treatment significantly inhibited collar-induced intimal thickening at day 14. The placement of the collar around the carotid artery decreased maximum contractile responses against contractile agents (KCl, phenylephrine, 5-hydroxytryptamine). The effect of the collar on contractile responses was enhanced as days elapsed. Decreased contractile responses of collared carotid arteries normalized at day 14 in the vitamin C treatment group. Vitamin C treatment also restored sensitivity to phenylephrine. The collar also significantly decreased acetylcholine-induced relaxations at day 3 and day 7. Acetylcholine-induced relaxations normalized in collared-arteries in the placebo group at day 14. Vitamin C treatment significantly increased acetylcholine-induced relaxations of both normal and collared carotid arteries at day 14. MMP-9 expression increased in collared arteries at day 3 and day 7 but did not change at day 14. MMP-2 expression increased in collared arteries at day 14. However, vitamin C treatment reduced collar-stimulated expression of MMP-2 at day 14. These findings indicate that vitamin C may have potentially beneficial effects on the early stages of atherosclerosis. Furthermore these results, for the first time, may indicate that vitamin C can also normalize decreased contractile response through perivascular collar placement.
维生素C具有高效的抗氧化特性,并参与诸如胶原蛋白合成等重要生理过程。因此,维生素C缺乏会导致严重并发症,包括血管疾病。本研究的目的是调查维生素C治疗对套环诱导的内膜增厚的影响。给兔子喂食正常胆固醇饮食,并在其左颈动脉周围放置非闭塞性硅套环,持续3天、7天和14天。兔子接受或不接受维生素C(150毫克/千克/天)治疗。套环诱导的内膜增厚在第7天变得明显。套环对内膜增厚的影响在第14天更为显著。维生素C治疗在第14天显著抑制了套环诱导的内膜增厚。在颈动脉周围放置套环会降低对收缩剂(氯化钾、去氧肾上腺素、5-羟色胺)的最大收缩反应。随着时间的推移,套环对收缩反应的影响增强。在维生素C治疗组中,套环颈动脉的收缩反应降低在第14天恢复正常。维生素C治疗还恢复了对去氧肾上腺素的敏感性。套环在第3天和第7天也显著降低了乙酰胆碱诱导的舒张反应。在安慰剂组中,套环动脉中乙酰胆碱诱导的舒张反应在第14天恢复正常。维生素C治疗在第14天显著增加了正常和套环颈动脉中乙酰胆碱诱导的舒张反应。基质金属蛋白酶-9(MMP-9)的表达在第3天和第7天在套环动脉中增加,但在第14天没有变化。基质金属蛋白酶-2(MMP-2)的表达在第14天在套环动脉中增加。然而,维生素C治疗在第14天减少了套环刺激的MMP-2表达。这些发现表明,维生素C可能对动脉粥样硬化的早期阶段具有潜在的有益作用。此外,这些结果首次表明,维生素C还可以通过血管周围放置套环使降低的收缩反应恢复正常。