Reduction of lipid peroxidation with intraoperative superoxide dismutase treatment decreases intimal hyperplasia in experimental vein grafts.
Reduction of lipid peroxidation with intraoperative superoxide dismutase treatment decreases intimal hyperplasia in experimental vein grafts.
复制标题
术中超氧化物歧化酶治疗减少脂质过氧化，从而减少实验性静脉移植物的内膜增生。
DOI：
10.1006/jsre.1999.5647
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Hagen,PO
中科院分区：
文献类型：
--
作者：
Huynh,TT;Davies,MG;Trovato,MJ;Barber,L;Safi,HJ;Hagen,PO
背景静脉移植失败通常归因于内膜增生病变的发展。氧化应激与动脉粥样硬化的发生和发展有关。在这项研究中，我们研究了局部术中治疗与聚乙二醇化超氧化物歧化酶（PEG-SOD）对脂质过氧化反应和内膜增生的发展，在实验veinegrafts.Materials和methodsForty新西兰白色雄兔有一个右颈动脉间置旁路移植术使用同侧反向颈静脉的影响。16只动物接受局部PEG-SOD（4，100单位）治疗; 9只动物接受不含SOD的聚乙二醇（PEG）溶剂; 16只动物用作对照。采用比色法测定术后3 d移植静脉丙二醛（MDA）浓度和超氧化物歧化酶（SOD）活性。为了确定壁尺寸和血管功能，形态和等距张力的研究进行了28天的静脉grafts.ResultsMDA浓度增加了5.7倍（P < 0.05），在3天的控制静脉移植相比，未移植的颈静脉。与对照组相比，PEG-SOD治疗组术后3天静脉移植物中SOD活性升高5.0倍（P < 0.05），MDA浓度降低8倍（P < 0.05）。在28天时，与对照静脉移植物相比，PEG-SOD处理的内膜厚度减少了35%（54 ± 4 vs 83 ± 5; P < 0.001），而中膜厚度没有变化（77 ± 4 vs 88 ± 5; P = ns）。与对照组相比，PEG-SOD处理28天的静脉移植物对去甲肾上腺素、5-羟色胺、缓激肽、硝普钠和乙酰胆碱的血管舒张功能没有显著变化。单独与PEG治疗没有显着改变脂质过氧化，壁尺寸，或vasculatory function of vein grafts.ConclusionThis study demonstrates，intrinsic local treatment of vein grafts with PEG-SOD increases SOD activity and reduces lipid peroxidation for at least 3 days，resulting in reduced intimal hyperplasia at 28 days.这些研究结果进一步牵连静脉移植物的增生反应的氧化应激，并建议在预防静脉移植失败的PEG-SOD的潜在治疗作用。
BackgroundVein graft failure is commonly attributed to the development of intimal hyperplastic lesions. Oxidative stress has been implicated in the initiation and progression of atherosclerosis. In this study we examined the effects of local intraoperative treatment with polyethylene glycolated superoxide dismutase (PEG-SOD) on lipid peroxidation and on the development of intimal hyperplasia in experimental vein grafts.Materials and methodsForty-one New Zealand White male rabbits had a right carotid interposition bypass graft using the ipsilateral reversed jugular vein. Sixteen animals received local PEG-SOD (4,100 units) treatment; 9 animals received the polyethylene glycol (PEG) vehicle without SOD; 16 animals were used as controls. Postoperatively, malondialdehyde (MDA, a product of lipid peroxidation) concentration and SOD activity were assessed in 3-day vein grafts by colorimetric spectrophotometry. To determine wall dimensions and vasomotor function, morphometric and isometric tension studies were performed on 28-day vein grafts.ResultsMDA concentration was increased 5.7-fold (P < 0.05) in 3-day control vein grafts compared to ungrafted jugular veins. Intraoperative PEG-SOD treatment raised SOD activity 5.0-fold (P < 0.05) and reduced MDA concentration 8-fold (P < 0.05) in 3-day vein grafts compared to controls. At 28 days, intimal thickness was reduced by 35% with PEG-SOD treatment (54 ± 4 vs 83 ± 5; P < 0.001) compared to control vein grafts, without a change in medial thickness (77 ± 4 vs 88 ± 5; P = ns). The vasomotor functions of 28-day PEG-SOD-treated vein grafts to norepinephrine, serotonin, bradykinin, nitroprusside, and acetylcholine were not significantly changed when compared to controls. Treatment with PEG alone did not significantly alter lipid peroxidation, wall dimensions, or vasomotor function of vein grafts.ConclusionThis study demonstrates that intraoperative local treatment of vein grafts with PEG-SOD increases SOD activity and decreases lipid peroxidation for at least 3 days, resulting in reduced intimal hyperplasia at 28 days. These findings further implicate oxidative stress in the hyperplastic response of vein grafts and suggest a potential therapeutic role for PEG-SOD in the prevention of vein graft failure.