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