铜离子抑制猪冠脉支架植入后新生内膜形成及其机制

The emergence of percutaneous coronary intervention significantly improved the symptoms and prognosis in patients with coronary heart disease, drug-eluting stents further reduced the incidence of stent restenosis, but stent restenosis and stent thrombosis were not completely resolved. Excessive neointimal formation was one of the most important mechanisms of restenosis. Existing stents were difficult to inhibit neointimal proliferation and to improve endothelialization at the same time. The novel Cu-bearing metal stent could inhibit the proliferation of vascular smooth muscle cells and promote the proliferation and adhesion of endothelial cells, while down-regulated expression of MiR-221/222 had a similar effect. On the basis of that Cu-bearing metal stent can reduce lumen loss in the miniature pig coronary overstretch model in vivo, and copper ion can promote endothelial cell proliferation, migration in vitro, This study will evaluate neointimal and endothelialization level of stented artery through imaging and pathology methods, and evaluate MiR-221/222 and its downstream gene expression of the stented artery and cultured cells by molecular biology method. It is proposed that copper ions can inhibit the formation of neointima and promote endothelialization, possibly by regulating MiR-221/222 and its downstream genes. Carrying out this project will help to understand the physiopathological actions on of copper ions in vascular injury after stenting. It is possible to provide theoretical basis for improving novel stent exploitation and clinical application, further improving the prognosis of patients with coronary heart disease.

经皮冠脉介入治疗改善了冠心病患者的症状及预后,药物洗脱支架进一步降低了支架内再狭窄发生，但再狭窄及血栓形成并未完全解决。新生内膜过度形成是再狭窄的重要机制，现有支架难以抑制内膜形成同时改善内皮化。新型铜离子支架可抑制血管平滑肌细胞增殖、促进内皮细胞增殖和粘附，而MiR-221/222表达下调有类似作用。本研究在前期小型猪冠脉过度扩张模型中发现铜离子支架可减少管腔丢失、体外实验发现铜离子可促进内皮细胞增殖、迁移的基础上，通过影像、病理学方法评价新型支架植入段血管新生内膜及内皮化水平、分子生物学方法评价支架段血管及培养细胞MiR-221/222及其下游基因表达情况。拟证明铜离子可抑制新生内膜形成、促进内皮化，可能通过调控MiR-221/222及其下游基因实现。本研究的开展有助于了解铜离子在血管损伤后病生理学过程中的作用，有可能为新型支架的开发和应用提供理论依据，进一步改善冠心病患者预后。

经皮冠脉介入治疗改善了冠心病患者的症状及预后,药物洗脱支架进一步降低了支架内再狭窄发生，但再狭窄及血栓形成并未完全解决。新生内膜过度形成是再狭窄的重要机制，现有支架难以抑制内膜形成同时改善内皮化。新型铜离子支架可抑制血管平滑肌细胞增殖、促进内皮细胞增殖和粘附，而MiR-221/222表达下调有类似作用。本研究在前期小型猪冠脉过度扩张模型中发现铜离子支架可减少管腔丢失、体外实验发现铜离子可促进内皮细胞增殖、迁移的基础上，通过体外对人冠脉内皮细胞在含铜支架材料及对照组材料共孵育，发现新型含铜材料可促进内皮细胞增殖、抑制MiR-221、促进p57的表达，而对MiR-222及p27表达无显著影响。初步证明新型含铜材料促进冠脉内皮细胞增殖可能通过抑制内源性MiR-221的表达及下游p57相关通路调控。本研究的开展有助于了解铜离子在血管损伤后病生理学过程中的作用，有可能为新型支架的开发和应用提供理论依据，进一步改善冠心病患者预后。