甲氨蝶呤抑制兔颈动脉球囊损伤后新生内膜形成The effects of methotrexate on the neointimal formation after balloon injured arteries in rabbits
孟磊,高炜,喻卓,郭艳红,田清平,赵春玉
摘要(Abstract):
目的 探讨不同剂量甲氨蝶呤 (MTX)对血管损伤后新生内膜形成的影响。方法 制备兔颈动脉球囊损伤模型 ,动物随机分为对照组、MTX 0 5mg/kg、MTX 1 5mg/kg及MTX 5mg/kg组 ,每组 5~ 8只 ,采用肌肉注射方式给药 ,于术后 2周和 4周取材 ,分别进行伊文思染色观察内皮覆盖情况、增殖细胞核抗原 (PCNA)免疫组化染色和定量组织形态学分析。结果 MTX治疗组血管内膜面积、内膜 /中膜面积比值均显著低于对照组 ,内膜面积抑制率达 4 6 %~ 5 6 %,不同剂量MTX之间差异无显著性。内膜及中膜PCNA阳性细胞数目较对照组减少。伊文思蓝染色显示各组间内皮修复程度差异无显著性。结论 MTX能够有效地抑制球囊损伤后血管平滑肌细胞的增殖和新生内膜形成 ,在一定剂量范围内 ,MTX的作用无明显差异。
关键词(KeyWords): 再狭窄;甲氨蝶呤;内皮,血管
基金项目(Foundation):
作者(Author): 孟磊,高炜,喻卓,郭艳红,田清平,赵春玉
参考文献(References):
- 1LauAK ,LeichtweisSB ,HumeP ,etal.Probucolpromotesfunctionalreendothelializationinballoon injuredrabbitaortas.Circulation,2003,107:20312036.
- 2DurandE ,MallatZ ,AddadF ,etal.Timecoursesofapoptosisandcellproliferationandtheirrelationshiptoarterialremodelingandrestenosisafterangioplastyinanatheroscleroticrabbitmodel.JAmCollCardiol,2002,39:16801685.
- 3MalikN ,FrancisSE ,HoltCM ,etal.Apoptosisandcellproliferationafterporcinecoronaryangioplasty.Circulation,1998,98:16571665.
- 4FarbA ,HellerPF ,ShroffS ,etal.Pathologicalanalysisoflocaldeliveryofpaclitaxelviaapolymer coatedstent.Circulation,2001,104:473479.
- 5HirataS ,MatsubaraT ,SauraR ,etal.Inhibitionofinvitrovascularendothelialcellproliferationandinvivoneovascularizationbylow dosemethotrexate.ArthritisRheum,1989,32:10651073.
- 6MerkleCJ,MooreIM ,PentonBS ,etal.Methotrexatecausesapoptosisinpostmitoticendothelialcells.BiolResNurs,2000,2:514.
- 7徐卫亭,霍勇,陈明,等.雷帕霉素和甲氨蝶呤涂层支架预防支架内再狭窄的实验研究.中国介入心脏病学杂志,2004,12:99102.
- 8HuangY ,SaluK ,LiS ,etal.MethotrexateloadedSAEcoatedcoronarystentsreduceneointimalhyperplasiainaporcinecoronarymodel.Heart,2004,90:195199.
- 9WhiteJC ,GoldmanID .MethotrexateResistanceinanL1210celllineresultingfromincreaseddihydrofolatereductase,decreasedthymidylatesynthetaseactivity,andnormalmembranetransport.JBiolChem,1981,256:57225727.