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Effects of stent-based delivery of rapamycin and methotrexate on neointimal formation in a porcine coronary model
徐卫亭,霍勇,陈明,洪涛,李拥军,高炜
摘要(Abstract)：
目的 评价雷帕霉素涂层支架、甲氨蝶呤涂层支架以及雷帕霉素和甲氨蝶呤混合涂层支架抑制血管新生内膜的作用和预防支架内再狭窄的有效性。方法 本实验采用随机、双盲试验 ,在2 5头微型猪的冠状动脉前降支或左旋支分别置入支架 1枚 ,其中金属裸支架 8枚、甲氨蝶呤涂层支架(每枚支架药物剂量 2 5 0～ 30 0 μg) 5枚、雷帕霉素涂层支架 (每枚支架药物剂量 6 8～ 96 μg) 7枚、雷帕霉素和甲氨蝶呤混合涂层支架 (每枚支架含雷帕霉素 5 8～ 81μg、甲氨蝶呤 12 0～ 170 μg) 5枚。 2 8d后进行冠状动脉造影随访 ,术后处死动物 ,取出支架血管 ,进行组织学分析。结果 再狭窄率 :对照组为2 5 % ( 2 8) ,甲氨蝶呤组为 80 % ( 4 5 ) ,其余 2组为 0。平均狭窄程度 :对照组为 31%± 2 2 % ,甲氨蝶呤涂层支架组为 6 4 %± 2 5 % (P <0 0 5 ) ,雷帕霉素涂层支架组为 8%± 17% (P <0 0 5 ) ,雷帕霉素和甲氨蝶呤混合涂层支架组为 3%± 4 % (P <0 0 5 )。新生内膜面积 :对照组为 ( 2 18± 1 0 3)mm2 ,甲氨蝶呤涂层支架组为 ( 3 93± 1 4 8)mm2 (P =0 0 6 9) ;雷帕霉素涂层支架组为 ( 0 94± 0 88)mm2 (P <0 0 5 ) ,雷帕霉素和甲氨蝶呤混合涂层支架组为 ( 0 4 7± 0 2 4 )mm2 (P <0 0 5 )。结论 在本实验中
关键词(KeyWords)： 支架;再狭窄;雷帕霉素;甲氨蝶呤
基金项目(Foundation):
作者(Author): 徐卫亭,霍勇,陈明,洪涛,李拥军,高炜
参考文献(References)：
- 1CronsteinBN .Themechanismofactionofmethotrexate.RheumDisClinNorthAm,1997,23:739755.
- 2PoonM ,MarxSO ,GgalloR ,etal.RapamycininhibitsVSMCmigration.JClinInvest,1996,98:22772283.
- 3MarxSO ,JayaramanT ,GoLO ,etal.RapamycinFKBPinhibitscellcycleregulatorsofproliferationinVSMC .CircRes,1995,76:412417.
- 4GregoryBM ,HuieP ,BillinghamME ,etal.Rapamycininhibitsarerialintimalthickeningcausedbybothalloimmuneandcytokineresponseininjury:itseffectoncellular,growthfactor,andcytokineresponseininjuredvessels.Transplantation,1993,55:14091418.
- 5GalloR ,PadureanA ,JauaramanT ,etal.Inhibitionofintimalthickeningafterballoonangioplastyinporcinecoronaryarteriesbytargetingregulatorsofthecellcycle.Circulation,1999,99:21642170.
- 6SuzukiT ,KopiaG ,HayashiS ,etal.Stent basdedeliveryofsirolimusreducesneointimalformationinaporcinecoronarymodel.Circulation,2001,4:11891193.
- 7FiresteinGS ,PaineMM ,BoyleDL .Mechanismsofmethotrexateactioninrheumatoidarthritis.ArthritisRheum,1994,37:193200.
- 8KremerJM .Themechanismsofactionofmethotrexateinrheumatoidarthritis.JRheumatol,1994,21:15.
- 9SegalR ,CaspiD ,TishlerM .etal.Shorttermeffectsoflowdosemethotrexateontheacutephasereactionsinpatientswithrheumatoidarthritis.JRheumatol,1989,16:914917.
- 10XianCoryJ ,CooljoC ,etal.EffectsofTGF alphageneknockoutonepithelialcellkineticsandrepairofmethotrexate induceddemageinmousesmallintestine.JCellPhysiol,2002,191:105115.
- 11Yoruk,Asim,Cizmecioglu,etal.Methotrexate inducedsystemicvasculitis.MedPediatrOncol,2002,38:139140.
- 12FarbA ,HellerPF ,ShroffS ,etal.Pathologicalanalysisoflocaldeliveryofpaclitaxelviaapolymer coatedstent.Circulation,2001,104:473479.