雌二醇洗脱支架抑制血管内膜增生的实验研究
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Estradiol eluting stent inhibits neointimal proliferation in rabbits abdominal aorta
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    摘要:

    目的观察雌二醇(E2)洗脱支架植入对高脂喂饲兔腹主动脉内膜增生的影响,并探讨其可能的机制。方法雄兔高脂喂饲后分别于腹主动脉植入裸金属支架、磷酸胆碱(PC)涂层支架和17β-E2洗脱支架,应用HE染色、免疫组化染色及蛋白印迹方法观察17β-E2洗脱支架抑制内膜增生的作用及机制。结果支架植入术后血管壁ERK迅速活化,磷酸化ERK(p-ERK)在术后0.5 h时达峰值。各组支架植入12周时血管内膜均明显增厚。E2洗脱支架组新生内膜面积较裸金属支架组减少36%。支架植入后0.5 h时E2洗脱支架组p-ERK表达明显低于裸金属支架组。2周时E2洗脱支架组内皮化率明显高于裸金属支架组及PC涂层支架组。结论 E2洗脱支架安全、有效,可明显减少实验兔支架植入后的血管内膜增生;与普通裸金属支架对比,E2洗脱支架能够加速支架段血管的再内皮化;丝裂原激活蛋白激酶ERK1/2可能介导了支架植入后血管平滑肌细胞的增殖和内膜增生。

    Abstract:

    Objective To evaluate the effects of 17β-estradiol(E2)-eluting stents on neointimal proliferation of abdominal aortas in high fat diet fed rabbits and to investigate the possible mechanism.Methods Male high fat diet fed rabbits received implantation of 17β-E2-eluting stents,or control phosphorylcholine coated stents or bare metal stents into abdominal aortas as control groups.Histology,immunohistochemistry and Western blot analysis were used to assess the inhibitive effects of E2-eluting stents on neointimal proliferation and and the possible mechanism.Results Western blot analysis revealed marked increase in ERK phosphorylation in 30 min after deployment of phosphorylcholine-coated or bare metal stents,indicating activation of MAP kinase pathway.Immunohistochemistry showed intense staining of phospho-ERK in the medial smooth muscle cells in stent-implanted region.Extensive neointimal hyperplasia developed 12 weeks after stenting.Neointimal area decreased by 36% in E2-eluting stent-implanted animals compared to bare metal stent-implanted animals.In E2-eluting stent-implanted animals,significant inhibition of ERK phosphorylation and neointimal thickening were observed and immunohistochemistry of factor Ⅷ-related antigen demonstrated an accelerated re-endothelialization as compared to the bare metal stent or phosphorylcholine-coated stent-implanted controls.Conclusion E2-eluting stents reduce neointimal proliferation and hence prevent restenosis after angioplasty,possibly by inhibiting ERK activation in smooth muscle cells and promoting re-endothelialization.?更多

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梁明,韩雅玲,康建,闫承慧,邓杰,徐凯.雌二醇洗脱支架抑制血管内膜增生的实验研究[J].中华老年多器官疾病杂志,2010,9(5):454~459

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