Argatroban抑制颈动脉球囊损伤后新生内膜的形成  

Preventive effects of argatroban on neointimal formation after carotid balloon injury in rats

作　　者：张志文[1] 章翔[1] 蒋晓帆[1] 薛菁晖 柳本■二 永田泉 菊池晴彦 

机构地区：[1]第四军医大学西京医院神经外科,西安710032 [2]西安交通大学 [3]日本国立循环器病中心脑血管外科

出　　处：《中华神经外科疾病研究杂志》2002年第1期68-71,共4页Chinese Journal of Neurosurgical Disease Research

基　　金：日本(竹世)川基金会资助项目

摘　　要：目的 观察特异性凝血酶抑制因子argatroban对颈动脉损伤后新生内膜形成的影响,探讨血管损伤后内膜增生、引起管腔狭窄的可能机制。方法32只SD大鼠于颈动脉球囊损伤后,经皮下埋置的渗透性微泵注射argatroban,分为高剂量组:40mg/周,n=9;中剂量组:20mg/周,n=6;低剂量组:10mg/周,n=8。对照组同法注射同体积的生理盐水,n=9。持续静脉给药1周。2周后检测颈动脉冠状切面新生内膜面积、新生内膜与中膜的面积比（NI/M）。结果中、高剂量治疗组的NI/M分别为1.00±0.11和1.08±0.09,明显低于对照组的1.46±0.11（P<0.05）;免疫染色显示伤后1周治疗组新生内膜血小板衍生生长因子（PDGF）-BB表达较对照组弱。结论 凝血酶在血管损伤后新生内膜形成的病理机制中发挥重要作用;特异性凝血酶抑制因子argatroban可能有助于预防颈动脉狭窄血管成形术后发生的再狭窄。Objective To understand the mechanism of neointimal formation after vascular injury, we examined the effect of specific thrombin inhibitor, argatroban, on neointimal formation in the carotid artery of rats after balloon injury. Methods Thirty - two male SD rats underwent balloon dilatation injury of the carotid artery to induce neointimal formation. Three groups of the animals were treated with intravenous infusion, using an osmotic mini pump, of the following doses of argatroban in 2 ml of saline for a week respectively: high dose, 40mg/wk ( n = 9 ) ; medium dose, 20mg/wk ( n = 6); low dose, 10mg/wk ( n = 8 ) . The control group (n = 9 ) was similarly treated with 2 ml of saline. Two weeks later, the injured carotid arteries were perfusion -fixed, and the area of the neointimal, medial layer and their ratios were analyzed under a microscope. Results Morphometric analysis revealed that there were significant differences in the intima - media ratio between the control and medium or high dose of argatroban groups (1.46±0.11; 1.00±0. 11 and 1.08±0.09, P<0.05). Hisloloigical study demonstrated that argatroban suppressed the production of platelet - derived growth factor (PDGF) - BB in the neointima and the medial smooth muscle cells layer. Conclusion Thrombin plays an essential role in pathological thickening of the arterial wall after balloon injury. The specific thrombin inhibitor, argatroban, may prevent restenosis after interventional therapy of carotid narrowing.

关 键 词：凝血酶 颈动脉狭窄 血小板源生长因子 大鼠 

分 类 号：R543.4[医药卫生—心血管疾病]