抗氧化治疗可逆转高胆固醇血症兔移植愈合受损。
Antioxidant therapy reverses impaired graft healing in hypercholesterolemic rabbits.
机构信息
Department of Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195, USA.
出版信息
J Vasc Surg. 2010 Jan;51(1):184-93. doi: 10.1016/j.jvs.2009.08.061. Epub 2009 Nov 24.
OBJECTIVE
Limited endothelial cell (EC) coverage and anastomotic intimal hyperplasia contribute to thrombosis and failure of prosthetic grafts. Lipid accumulation and lipid oxidation are associated with decreased EC migration and intimal hyperplasia. The goal of this study was to assess the ability of antioxidants to improve graft healing in hypercholesterolemic animals.
METHODS
Rabbits were placed in one of four groups: chow plus N-acetylcysteine (NAC), chow plus probucol, chow with 1% cholesterol plus NAC, or chow with 1% cholesterol plus probucol. After 2 weeks, expanded polytetrafluoroethylene grafts (12 cm long x 4-mm internal diameter) were implanted in the abdominal aorta. Grafts were removed after 6 weeks and analyzed for cholesterol content, EC coverage, anastomotic intimal thickness, and the cellular composition of the neointima. Plasma samples were obtained to assess systemic oxidative stress. The data were compared with previously reported data from animals fed diets of chow and chow with 1% cholesterol.
RESULTS
Prosthetic grafts from rabbits fed chow with 1% cholesterol had significantly greater anastomotic intimal thickening and lower EC coverage than grafts from rabbits fed a regular chow diet. In hypercholesterolemic rabbits, antioxidant therapy decreased global oxidative stress as evidenced by a 40% decrease in plasma thiobarbituric acid reactive substances. In rabbits fed the chow with 1% cholesterol diet, NAC decreased intimal hyperplasia at the proximal anastomosis by 29% and significantly increased graft EC coverage from 46% to 71% (P = .03). Following a similar pattern, probucol decreased intimal hyperplasia by 43% and increased graft EC coverage to 53% in hypercholesterolemic rabbits.
CONCLUSIONS
Global oxidative stress and anastomotic intimal hyperplasia are increased, and endothelialization of prosthetic grafts is significantly reduced in rabbits fed a high-cholesterol diet. Antioxidant treatment improves EC coverage and decreases intimal hyperplasia. Reducing oxidative stress may promote healing of prosthetic grafts.
目的
内皮细胞（EC）覆盖不足和吻合口内膜增生导致假体移植物血栓形成和失败。脂质积累和脂质氧化与 EC 迁移和内膜增生减少有关。本研究的目的是评估抗氧化剂改善高胆固醇血症动物移植物愈合的能力。
方法
将兔子分为四组：普通饲料加 N-乙酰半胱氨酸（NAC）、普通饲料加普罗布考、普通饲料加 1%胆固醇加 NAC 或普通饲料加 1%胆固醇加普罗布考。2 周后，将膨胀聚四氟乙烯移植物（12 cm 长×4-mm 内径）植入腹主动脉。6 周后取出移植物，分析胆固醇含量、EC 覆盖率、吻合口内膜厚度和新生内膜的细胞组成。采集血浆样本评估全身氧化应激。将数据与之前报道的给予普通饲料和 1%胆固醇饲料的动物的数据进行比较。
结果
给予 1%胆固醇普通饲料的兔子的假体移植物吻合口内膜增厚明显，EC 覆盖率明显低于给予普通饲料的兔子。在高胆固醇血症的兔子中，抗氧化治疗可降低全身氧化应激，表现为血浆硫代巴比妥酸反应物减少 40%。在给予 1%胆固醇饮食的兔子中，NAC 使近端吻合口内膜增生减少 29%，并使移植物 EC 覆盖率从 46%显著增加至 71%（P=0.03）。类似地，普罗布考使高胆固醇血症兔子的内膜增生减少 43%，并将移植物 EC 覆盖率增加至 53%。
结论
高胆固醇饮食可增加兔子的全身氧化应激和吻合口内膜增生，显著降低假体移植物的内皮化。抗氧化治疗可改善 EC 覆盖率，减少内膜增生。降低氧化应激可能促进假体移植物的愈合。
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