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葛根素涂层支架对再狭窄的防治及其分子机制研究
【作者】 柴欣楼；
【导师】 王伟；
【作者基本信息】 北京中医药大学 ， 中西医结合基础， 2006， 博士
【摘要】 一、研究背景冠状动脉粥样硬化性心脏病(冠心病)的高死亡率和高致残率,已成为严重危害我国人民健康的主要疾病,因此加强对冠心病的研究,具有极大的必要性和迫切性。支架安置术作为经皮冠状动脉内球囊扩张成形术(percutaneous transluminal coronary angioplasty, PTCA)后的补充用于临床,有效降低了PTCA术后再狭窄的发生率。但支架安置术后支架内再狭窄ISR(in-stent restenosis, ISR)发生率仍高达15%～20%。其发病的病理机制为:支架植入过程可使内皮细胞损伤,受损的内皮细胞可促进附壁血栓的形成,同时释放各种血管活性物质、生长因子、粘附分子,如单核细胞趋化蛋白-1(monocyte chemoattractant protein-1, MCP-1),白介素-6(interleukin,IL-6)、粘附分子细胞间粘附分子-1(intercellular adhesion molecule,ICAM-1)、血管细胞粘附分子-1(vascular cell dhension molecule,VCAM-1)等。这些细胞因子可促进血管收缩,促进血管平滑肌细胞(vessel smooth musle cell, VSMC)由中膜迁移到内膜并增殖,同时启动一系列血管损伤后修复反应,促进内膜增厚,形成支架内再狭窄。因此,血栓形成、内膜增厚、血管重塑三个时期构成ISR的发病主要病理过程。目前临床应用的药物涂层支架主要有雷帕霉素涂层支架及紫杉醇涂层支架。紫杉醇通过阻止微管断裂,造成细胞凋亡而抑制VSMC增殖,从而抑制内膜增殖;但其在血管壁内的长期存在可导致动脉血管壁坏死和动脉瘤形成,阻碍了其在临床的广泛应用。雷帕霉素可使细胞分裂受阻于G1期而不能进入S期,抑制VSMC细胞增殖,大大降低了ISR的发生率,但发生晚期血栓的几率较高,可能与其抑制内皮细胞增殖,导致内皮细胞修复时间延长有关。同时,雷帕霉素涂层支架的价格远远超出了我国普通大众的经济承受能力,因而有必要寻求一种适合我国生活水平且疗效较好的药物涂层支架。葛根素(Puerarin, Pur)为异黄酮类化合物,属于植物雌激素,现代药理研究证明,葛根素在心血管中具有多种功能,主要有抗血小板活性,改善纤溶酶活
【Abstract】 BACKGROUNDCoronary heart disease (CHD)has a high mortality and mutilation rate, it is the cause of one of every five deaths each year in China, becoming a main disease do harm to the people’s health badly. It remains a persistent public health burden in China, and to enhance the study on CHD is very important and necessarily. Stent as the supplement to prevent the restenosis after percutaneous transluminal coronary angioplasty (PTCA), can reduce the percent of restenosis, but there still has 15-20% in the In-Stent Restenosis (ISR). The main pathogenesis of the ISR maybe exist as below: the damage of endothelium cell during the stent insertion, and the hurt can promote the formation of mural thrombus, releasing angio-activity substance such as growth factor, adhesive factor and so on. All of these cytokine can contract the vessel and migration and proliferation of the smooth muscle cell. In the same time they can promote the vasoconstriction and proliferation of vessel smooth musle cell (VSMC), promoting the vessel repair after damage, and induce proliferation of endometrium and formation of ISR. So thrombosis, proliferation of endometrium and formation of new endometrium, blood vessel-remodeling is the three processes of ISR.The drug-eluting stents (DES) mainly used in clinic are Rapamycin eluting stent and Paclitaxel Eluting Stent. Paclitaxel is a kind of anti-tumour drug; it can prevent the division of the cell and promote the apoptosis of cell. But it also have cell-toxin effect and induce the occurrence of apoptosis of artery walls and aneurysm,which inhabit the application in clinic. Rapamycin eluting stent can prevent the expression of cell cycle protein and complex of cyclin dependent kinase (CDK), it can make the division of cell stop at the G1 to S step, and prevent the proliferation of the cell, thus can reduce the opportunity of ISR, but the rate of the thrombosis is high in the late period. Other more, All the two DES is too expensive for the patient in our country, so it is very important to made a new DES fitting for our living standard and having good effect.