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经皮腔内血管成形术(PTA)是治疗冠状动脉及周围动脉狭窄的有效手段,但约有25%～60%的病人术后发生再狭窄。金属内支架的应用降低了PTA术后急性闭塞的发生率,但并未能彻底解决再狭窄的问题代写论文。大量实验研究及临床观察表明再狭窄与血栓形成、内膜增厚和血管重构有关,内皮细胞的损伤、修复及功能改变在其中扮演重要角色。
一、内皮损伤、血栓形成与再狭窄
PTA可造成血管损伤，内皮的剥脱造成内皮下组织的暴露,血小板立即通过Von Willebrand因子（VWF）黏附于内皮下的基质,随后发生聚集并释放α颗粒成分,其释放的血小板衍生生长因子(PDGF)可能与中膜平滑肌细胞的激活和迁移有关［1］。最近的研究表明血小板减少可抑制已激活的平滑肌细胞从中膜向内膜迁移。由内皮损伤引发的凝血过程将形成附壁血栓,血栓的形成不仅可造成血管的急性闭塞,而且为平滑肌细胞内迁提供了框架,血栓的机化可直接引起内膜增厚,而且血栓中的凝血酶本身就是强力的平滑肌细胞致分裂原［2］。实验证明损伤部位内皮的早期重建可抑制血小板附着和血栓形成［3］。
二、内皮细胞和内膜增厚
血管损伤后出现的组织愈合反应可造成不同程度的内膜增厚,其中包括3种主要成分:平滑肌细胞、内皮细胞及细胞外基质。损伤后30分钟就可以检测到平滑肌细胞早期激活的标记——核原癌基因的表达［4］, 活化的平滑肌细胞从收缩表型转向合成表型，从而引发平滑肌细胞的增生迁移和基质的合成。平滑肌细胞增生后向内膜迁移，迁移到内膜的平滑肌细胞部分继续增生。有作者认为平滑肌细胞的增生和分裂是两个不同的机制［5］，一些因素只影响其中一个而不影响另一个， PDGF是平滑肌细胞向内膜迁移强力的趋化因子，成纤维细胞生长因子b（bFGF）则是平滑肌细胞的致分裂原。平滑肌细胞要穿过细胞外基质和弹力层才能到达内膜，其迁移过程与纤维蛋白溶解酶原激活物及金属蛋白酶（MMP）的增加有关。
三、内皮细胞与血管重构
四、内皮细胞损伤、修复及功能异常
五、加快重内皮化、促进内皮细胞功能恢复
蛋白激酶C （PKC）是广泛存在于细胞内的信号传递物质，是内皮细胞增殖所必需的,用12-豆蔻酸-13-乙酸佛波酯直接活化内皮细胞PKC，发现内皮细胞黏附、伸展及移行能力均增强，而用PKC抑制剂则降低了内皮细胞的再生能力，可见PKC激活剂可作为促进重内皮化的一种方法。
六、金属内支架和血管内皮化
金属内支架的应用大大减低了PTA术后的急性动脉闭塞，其形态稳定性限制了血管的回缩，从而防止了不利的血管重构，但金属内支架本身具致凝性，置入血管后需长期抗凝治疗，而且内支架置入并未彻底解决再狭窄的问题，目前认为PTA术后再狭窄是内膜增生和血管重构双重作用的结果，而内支架置入后再狭窄则主要由内膜增生引起［26］。为阻止内膜增厚，许多学者用带有涤纶被膜的内支紲进行实验研究和临床探索，但一直没有肯定的结果，Schurmann等［27］的实验研究发现，与普通支架相比，被膜式支架引起了更严重的内膜增生和炎症反应；
Maynar等［28］的一组股动脉临床资料也表明被膜式支架的通畅率并不理想。支架置入部位的早期内皮化可能预防血栓形成和再狭窄。加速支架内皮化的方法目前主要有两种,一是支架置入后局部灌注药物或导入基因,常用的是VEGF；
另一方法是支架置入前在体外先种上内皮细胞［29-31］，可选用转基因内皮细胞进行种植［30，31］，此法最大的障碍是支架置入过程中内皮细胞的丢失［30，31］，但支架金属丝侧面往往有内皮细胞残留，这些细胞可重新增殖并覆盖支架［15,31］。
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