Porter K E, Loftus I M, Peterson M, Bell P R, London N J, Thompson M M
Department of Surgery, University of Leicester, Leicester Royal Infirmary, UK.
Br J Surg. 1998 Oct;85(10):1373-7. doi: 10.1046/j.1365-2168.1998.00888.x.
There is now accumulating evidence that matrix metalloproteinases (MMPs), the physiological mediators of matrix deposition and degradation, play an important role in the development of intimal hyperplasia following arterial bypass. This study investigated the effect of marimastat, an orally active specific MMP inhibitor, on neointima formation in cultured human saphenous vein.
Segments of human saphenous vein obtained from ten patients undergoing arterial bypass surgery were cultured for 14 days in serum-supplemented RPMI medium (controls) or in control medium supplemented with marimastat at three different concentrations (treatment groups). Following culture, half of each segment was prepared for histological examination and MMPs were extracted from the other half for gelatin zymography.
Marimastat inhibited neointimal thickening in a concentration-dependent manner; inhibition was significant at 10(-5) and 10(-6) mol/l (P=0.006). This observation was paralleled by a significant reduction in the levels of MMP-2 and MMP-9 in the tissues.
Marimastat significantly reduced neointimal thickening in this laboratory model. MMP inhibitors may offer a potential therapeutic strategy in the prevention of intimal hyperplasia.
目前有越来越多的证据表明，基质金属蛋白酶（MMPs）作为基质沉积和降解的生理介质，在动脉搭桥术后内膜增生的发展过程中起重要作用。本研究调查了口服活性特异性MMP抑制剂马立马司他对培养的人隐静脉内膜形成的影响。
从10例接受动脉搭桥手术的患者获取人隐静脉段，在补充血清的RPMI培养基（对照组）或补充三种不同浓度马立马司他的对照培养基（治疗组）中培养14天。培养后，每段静脉的一半用于组织学检查，另一半提取MMPs用于明胶酶谱分析。
马立马司他以浓度依赖性方式抑制内膜增厚；在10^(-5)和10^(-6) mol/L时抑制作用显著（P = 0.006）。这一观察结果与组织中MMP-2和MMP-9水平的显著降低相平行。
在该实验室模型中，马立马司他显著降低了内膜增厚。MMP抑制剂可能为预防内膜增生提供一种潜在的治疗策略。
