阿托伐他汀合用白藜芦醇对药物洗脱支架置入后内皮化的影响及机制研究

Long term outcomes from randomized clinical trials have shown the persisting benefit of the drug eluting stents (DES) in inhibiting neointimal hyperplasia and subsequent restenosis, as compared to the bare metal stent (BMS). However, thrombosis remains the most critical issue of modern DES utilization. The delayed re-endothelialization due to DES implantation is the main reason of stent thrombosis. Our study has found that Atorvastatin, which is commonly used in the clinical treatment of coronary heart disease, can accelerate the re-endothelialization after DES implantation, but the incidence of thrombosis remains high. Previous studies suggested that Resveratrol can be extracted from daily common foods and it can mediate signalling pathways that are different from or identical with Atorvastatin , among which PI3K/AKT and SIRT 1 are representative, to accelerate the re-endothelialization after DES implantation. Therefore, we proposed a hypothesis that Atorvastatin combined with Resveratrol can further speed up the re-endothelialization after DES implantation. We designed a randomized controled study using an atherosclerotic animal model which can mimic the clinical condition better to verify our hypothesis and study the molecular biological mechanism of the novel combined utilization of Atorvastatin and Resveratrol after DES implantation . After 6 weeks' High-fat feeding,when the atherosclerotic model is established , DES will be implanted in each group in company with different medication . And we will isolate the endothelial progenitor cells(EPC) from blood and analysis EPC's proliferation, migration and adhesion function before DES implantation as well as 14days、28days after DES implantation respectively. Meanwhile,we will keep observing the extent and rate of the re-endothelialization after DES implantation, and try to study how Resveratrol consolidates the benefit of Atorvastatin in accelerating re-endothelialization using the acquired EPCs through some modern biological technologys. All in all, so long as we got the hypothesis that Atorvastatin combined with Resveratrol can further accelerate the re-endothelialization after DES implantation approved, it would make great sense in reducing thrombosis incidence and the course of dual antiplatelet theropy and ultimately economizing the medical resources in the foreseeable future.

药物涂层支架（DES）置入后内皮化不全导致的血栓(ST)形成产生重大危害。虽然我们前期研究发现广泛应用于临床的阿托伐他汀可以加快DES置入后血管再内皮化，但并不足以降低 ST的发生。既往研究提示食物提取物白藜芦醇可通过与阿托伐他汀共同（PI3K/AKT）或不同（SIRT 1）的信号通道促进损伤血管内皮化。因此我们假设：阿托伐他汀与白藜芦醇合用可进一步加快DES置入后血管再内皮化以降低ST发生。本研究采用更贴近临床的动脉粥样硬化动物模型并置入DES，分析二者合用促进DES置入后血管再内皮化的作用及机制：首先，分离不同处理组的内皮祖细胞，分析内皮祖细胞增殖、迁移及黏附功能变化；然后，利用分离的内皮祖细胞，分析可能促进内皮化的机制，最后，检测对内皮化速率、内膜覆盖程度的作用。若能证实假说，可望应用于临床降低DES置入后ST发生并缩短抗血小板药物时间，具有重要临床及卫生经济学意义。