【摘要翻译】昔洛他唑对白细胞整合素Mac-1抑制作用可能减少冠脉支架术后再狭窄

【题目】 Cilostazol inhibits leukocyte integrin Mac-1, leading to a potential reduction in restenosis after coronary stent implantation
【作者】Teruo Inoue MD, FACC*, †, , , Toshihiko Uchida MD†, Masashi Sakuma MD†, Yo***aka Imoto‡, Yasushi Ozeki PhD§, Yukio Ozaki MD§, Yutaka Hikichi MD* and Koichi Node MD*
【单位】*Department of Cardiovascular and Renal Medicine, Saga University Faculty of Medicine, Saga, Japan
†Department of Cardiology, Koshigaya Hospital, Dokkyo University School of Medicine, Koshigaya, Japan
‡Yufu Itonaga Company, Tokyo, Japan
§Department of Laboratory Medicine, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Tamaho, Japan
【文献来源】Journal of the American College of Cardiology Volume 44, Issue 7 , 6 October 2004, Pages 1408-1414
【摘要】
Objectives
The aim of this study was to confirm clinically a hypothesis that cilostazol inhibits leukocyte Mac-1, leading to prevention of post-stent restenosis.
Background
The platelet phosphodiesterase III inhibitor called cilostazol also inhibits alpha-granule release of P-selectin in platelets. The P-selectin–mediated platelet-leukocyte interaction promotes activation and upregulation of leukocyte Mac-1 after coronary stenting, which plays a key role on the mechanism of restenosis. Thus, cilostazol's potential inhibition of this process may lead to prevention of restenosis.
Methods
Using flow cytometric analysis of whole blood obtained from the coronary sinus, the expression of platelet membrane glycoproteins and neutrophil adhesion molecules was observed in 70 consecutive patients undergoing coronary stenting. The patients were randomly assigned to either a cilostazol or ticlopidine group before stent placement.
Results
The restenosis rate was lower (15% vs. 31%, p < 0.05) in the cilostazol group (n = 34) than in the ticlopidine group (n = 32). A stent-induced increase in platelet P-selectin (CD62P) expression and an increase in neutrophil Mac-1 (CD11b) expression were suppressed in the cilostazol group compared with the ticlopidine group. Angiographic late lumen loss was correlated with the relative changes in platelet P-selectin and neutrophil Mac-1 at 48 h after coronary stenting.
Conclusions
Cilostazol may have effects on suppression of P-selectin–mediated platelet activation, platelet-leukocyte interaction, and subsequent Mac-1–mediated leukocyte activation, which might lead to a reduced restenosis rate after coronary stent implantation.
【翻译】
目的：本研究目的在于证实临床上有关昔洛他唑对白细胞Mac-1具有抑制作用，进而预防冠脉支架术后再狭窄的假设。
背景：血小板磷脂酶III抑制剂昔洛他唑（培达）还可以抑制血小板α颗粒释放P选择素，由后者介导的血小板-白细胞的相互作用促进了冠脉支架术后白细胞Mac-1的活化和上调，而这又在再狭窄机制方面起重要作用。因而昔洛他唑对此过程潜在的抑制作用可能会预防再狭窄的发生。
方法：70例患者接受冠脉支架术中自冠状窦采取全血标本，应用流式细胞分析技术观察血小板膜糖蛋白和中性粒细胞黏附因子的表达情况。患者在置入支架前被随机分配到昔洛他唑或抵克利得组。
结果：昔洛他唑组(n = 34)再狭窄率低于抵克利得组(n = 32) (15% vs.31%, p < 0.05)。与抵克利得组相比，昔洛他唑组患者由于支架诱导的血小板P选择素(CD62P)以及中性粒细胞Mac-1的表达得到抑制。血管造影显示，支架术后48小时的晚期管腔丢失与血小板P选择素以及中性粒细胞Mac-1的相对变化有关。
结论：昔洛他唑可以对P选择素介导的血小板活化、血小板-白细胞的相互作用以及随后Mac-1介导的白细胞活化有抑制效应，这可能降低支架置入术后的再狭窄率。
【评论】
支架术后的再狭窄问题，给介入治疗带来了不可避免的难题，人们已从多方面探讨降低再狭窄率的方法。药物洗脱支架（DES）较好的解决了这方面的问题，但其费用较高，本研究的发现从费用-效益比方面对DES提出了挑战，拓宽了解决再狭窄问题的思路。