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紫杉醇局部治疗抑制猪静脉桥新生内膜形成和增厚的实验研究 被引量:2

Inhibition of Vein Graft Neointima Formation in Porcine Models by Paclitaxel
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摘要 目的 :局部药物治疗是一个很好的防治静脉桥病变的策略。本研究用抗细胞增殖药物紫杉醇处理大隐静脉桥后植入猪的颈动脉 ,以观察紫杉醇的抗细胞增殖作用在抑制静脉桥内膜平滑肌细胞增殖、迁移导致内膜形成和增厚的效果。方法 :将 10头猪的 2 0只大隐静脉桥分为两组。治疗组 :将大隐静脉桥 10只置于含有 10 μmol/L浓度的紫杉醇溶液中 (先用该溶液灌洗 )浸泡 1h后植入猪的颈动脉 ,紫杉醇是溶解在 2 5 μl/L的无水酒精中 ,对照组 10只大隐静脉桥置于单纯的酒精中浸泡。 4周后取开放的静脉桥进行组织学分析。结果 :①治疗组静脉桥新生内膜面积 (1 5 9± 0 95 )mm2 ,对照组新生内膜面积高达 (2 43± 1 3 5 )mm2 ,治疗组显著低于对照组 ,两组比较有非常显著的差异 ,P <0 0 1;②治疗组内膜平滑肌细胞密度均值为 (3 681± 193 5 ) /mm2 ,对照组为 (4 60 7± 1993 ) /mm2 ,两组比较有显著性差异 ,P <0 0 5 ;中膜平滑肌细胞密度均值治疗组 (2 13 9± 73 4) /mm2 ,对照组(3 62 9± 3 2 0 7) /mm2 ,两组比较有显著性的差异 ,P <0 0 5。结论 :紫杉醇可显著抑制静脉桥内膜、中膜平滑肌细胞的增殖 ,抑制新生内膜的形成 ,证明紫杉醇可在防治静脉桥闭塞方面发挥独特作用。 Objective: Following early thrombosis,10%-15% of coronary vein grafts fail within 5 years due to intima thickening. Paclitaxel is a potent inhibitor of cell proliferation by inducing a sustained block of mitosis at the metaphase/anaphase boundary. Paclitaxel also enhances the assembly of stable microtubules,which have a role in cell migration. This study investigated the effect of Paclitaxel pre-treatment of saphenous vein on neointima formation in a porcine model of saphenous vein to carotid artery interposition grafting. Methods: Large white pigs ( n =10,25.0-33.5 kg) underwent bilateral saphenous vein to carotid artery interposition grafting. The vein grafts were pre-treated in the solution for 1 hour at room temperature with paclitaxel (10 μmol/L) or vehicle control,prior to anastomosis as an end-to-end interposition graft,into the common carotid artery. Each animal received a treated and a control graft. Animals were sacrificed at 28 days. Vein grafts were pressure-fixed at 100 mmHg prior to histological preparation and morphometric analysis. Statistical analysis was performed using unpaired two-tailed Student t test. Significance was considered when p <0.05. Rusults: The neointima area in the treated group was (1.59±0.95) mm 2,significantly smaller than that of the control (group(2.43±1.35)mm 2,p <0.01).In the treated group,the smooth muscle cell density was(3681±1935)/mm 2 in intima and (2139±734)/mm 2 in media,remarkably smaller when compared with the control ((4607±1993)/mm 2, p <0.05 and (3629± 3207)/mm 2, p <0.05;respectively).Conclusion: Our data demonstrate that paclitaxel pre-treatment reduces neointima formation in porcine interposition grafts at 28 days. Paclitaxel may be a highly attractive candidate for prevention of neointima formation and late vein graft failure.
出处 《中国循环杂志》 CSCD 北大核心 2003年第6期465-467,共3页 Chinese Circulation Journal
基金 英国心脏基金会资助
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  • 1[1]Izzat MB, Angelini GD. Arterial conduits in myocardial revascularization. Surgery, 1994,12:37-41.
  • 2[2]Weintraub WS, Jones EL, Craver JM,et al. Frequency of repeat coronary bypass or coronary angioplasty after coronary artery bypass surgery using saphenous venous grafts. Am J Cardiol, 1994, 73:103-112.
  • 3[3]Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature, 1979, 277:665-667.
  • 4[4]Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst, 1990, 82:1247-1259.
  • 5[5]Sollott SJ, Cheng L, Pauly RR, et al. Taxol inhibits neointimal smooth muscle cell accumulation after angioplasty in the rat. J Clin Invest,1995, 95: 1869-1876.
  • 6[6]Axel DI, Kunert W, Goggelmann C, et al. Paclitaxel inhibits arterialsmooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation, 1997, 96: 636-645.
  • 7[7]Farb A, Heller RF, Carter AJ, et al. Paclitaxel polymer-coated stents reduce neointima. Circulation, 1997, 96: 1608.
  • 8[8]Hoffmann R, Mintz GS, Dussaillant GR, et al. Patterns and mechanisrns of in-stent restenosis: a serial intravascular ultrasound study. Circulation, 1996, 94:1247-1254.
  • 9[9]Fremes S, Levinton C, Naylor C, et al. Optimal antithrombotic thera-py following aortocoronary bypass: a meta-analyses. Eur J Cardiothorac Surg, 1993, 7:169-180.
  • 10[10]Mann MJ, Whittemore AD, Donaldson MC, et al. Ex-vivo gene therapy of human vascular bypass grafts with E2F decoy: the PREVENT single-cantre, randomized, controlled trial. Lancet, 1999,354:1493-1498.

同被引文献7

  • 1McDonnell PJ,Stark WJ,Green WR.Posterior capsule opacification:A specular microscopic study[J].Ophthalmology,1984,91(7):853-856.
  • 2Odrich MG,Hall SJ,worgul BV,et al.Posterior capsular opacification:experimental analysis[J].Ophthalmic Res,1985,17(2)∶75-84.
  • 3Serruys PW,Degertekin M,Tanabe K,et al.Vascular responses at proximal and distal edges of paclitaxel-eluting stents:serial intravascular ultrasound analysis from the TAXUS Ⅱ trial[J].Circulation,2004,109(5):627-633.
  • 4Goorin AM,Harris MB,Bemstein M,et al.Phase Ⅱ/Ⅲ trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma:a pediatric oncology group trial[J].J Clin Oncol,2002,20(2):426-433.
  • 5Oberhoff M,Herdeg C,Baumbach A,et al.Stent-based antirestenotic coatings (sirolimus/paclitaxel)[J].Catheter Cardiovasc Interv,2002,55(3):404-408.
  • 6Jampel HD,Moon JI.The effect of paclitaxel powder on glaucoma filtrtion surgery in rabbits[J].J Glaucoma,1998,7(3):170-177.
  • 7Pandey SK,Cochener B,Apple DJ,et al.Intracapsular ring sustained 5-fluorouracil delivery systm for the prevention of posterior capsule opacification in rabbits:A histological study[J].J Cataract Refract Surg,2002,28(1):139-148.

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