骨髓间充质干细胞对球囊损伤的大鼠颈总动脉内皮修复的影响Effect of bone marrow mesenchymal stem cells on repairment of carotid artery endothelium injured by balloon in rats
李玉巧,刘志忠,李小波,苏晓叶,吴俊,陈绍良
摘要(Abstract):
目的研究骨髓间充质干细胞对球囊损伤的大鼠颈总动脉内皮修复的影响。方法球囊损伤24只SD大鼠颈总动脉,建立动脉内皮损伤模型,随机分为:(1)治疗组12只SD大鼠,球囊损伤颈总动脉即刻注射1mL骨髓间充质干细胞溶液;(2)对照组12只SD大鼠,球囊损伤颈总动脉即刻注射1mL磷酸盐缓冲液。14d及28d后,取颈总动脉标本作组织病理切片,行苏木精伊红及血管内皮生长因子受体-2、α-平滑肌肌动蛋白免疫组化染色。结果用苏木精伊红染色观察新生内膜的厚度,14d及28d治疗组血管内膜增生均较对照组轻(14d时0.57±0.06cm比1.09±0.06cm,P<0.05;28d时0.43±0.09cm比4.72±0.15cm,P<0.05);用血管内皮生长因子受体-2免疫组化染色观察内皮化程度,治疗组血管内皮细胞覆盖程度高于对照组(14d时70.8%±1.3%比20.4%±1.1%,P<0.05;28d时90.2%±1.3%比10.7%±0.4%,P<0.05),治疗组可见血管内皮生长因子受体-2/5-溴脱氧尿核苷双阳性细胞约占血管内皮生长因子受体-2单阳性细胞的50%。α-平滑肌肌动蛋白免疫组化染色观察平滑肌细胞浸润积分,14d时治疗组平滑肌细胞浸润1.5分,对照组2分;28d时两组分别为1分和3分。结论骨髓间充质干细胞可减轻新生内膜增生,加快损伤血管的内皮化进程,减少平滑肌细胞浸润,从而促进球囊损伤的大鼠颈总动脉内皮完整性修复。
关键词(KeyWords): 间质干细胞;血管内膜;内皮细胞;肌细胞,平滑肌
基金项目(Foundation):
作者(Author): 李玉巧,刘志忠,李小波,苏晓叶,吴俊,陈绍良
参考文献(References):
- [1]Rafii S,Lyden D.Therapeutic stem and progenitor cell transplan.tation for organ vascularization and regeneration.Nat Med,2003,9:702.712.
- [2]Libby P,Sukhova G,Lee R,et al.Molecular biology of atheroscle.rosis.Int J Cardiol,1997,62:S23.S29.
- [3]Wu XJ,Huang L,Qi Z,et al.Mesenchymal stem cells participat.ing in ex vivo endothelium repair and its effect on vascular smooth muscle cells growth.Int J Cardiol,2005,105:2742.2748.
- [4]Hyun.Jai C,Hyo.Soo K,Myoung.Mook L,et al.Mobilized endo.thelial progentitor cells by granulocyte.Macrophage colony.stimu.lating factor accelerate reendothelialization and reduce vscular in.flammation after intravascular radiation.Circulation,2003,108:2918.2929.
- [5]Tim K,Eugenio S,Mary S,et al.Bone marrow.derived cells for enhancing collateral decelopment mechanisms,animal data,and initial clinical experiences.Circ Res,2004,95:354.361.
- [6]Kinnaird T,Stabile E,Burnett MS,et al.Marrow.derived stro.mal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms.Circ Res,2004,94:678.685.
- [7]Pipp F,Heil M,Issbrucker K,et al.VEGFR.1.selective VEGF homologue PlGF is arteriogenic:evidence for a monocyte.mediated mechanism.Circ Res,2003,92:378.385.
- [8]Buschmann I,Heil M,Jost M,et al.Influence of inflammatory cy.tokines on arteriogenesis.Micro Circ,2003,10:371.379.
- [9]Ton J,Hetty C,Eelco J,et al.Endothelial Progenitor Cells:More Than an Inflammatory Response?Arterioscler Thromb Vasc Biol,2004,24:834.838.
- [10]Zohlnhofer D,Klein CA,Richter T,et al.Gene expression profi.ling of human stent.induced neointima by cDNA array analysis of microscopic specimens retrieved by helix cutter atherectomy:De.tection of FK506.binding protein12upregulation.Circulation,2001,103:1396.1402.
- [11]Ainwright CL,Miller AM,Wadsworth RM.Inflammation as a key event in the development of neointima following vascular balloon injury.Clin Exp Pharmacol Physiol,2001,28:891.895.
- [12]Welt FGP,Edelman ER,Simon DI,et al.Not macrophage infiltra.tion precedes neointimal thickening in balloon.injured arteries.Arterioscler Thromb Vasc Biol,2000,20:2553.2558.
- [13]Luciano C,Anastasios P,Karl H,et al.Cardiac repair with in.tramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction.PNAS,2005,102:11474.11479.
- [14]Di Nicola M,Carlo Stella C,Magni M,et al.Human bone marrow stromal cells suppress T.lymphocyte proliferation induced by cel.lular or nonspecific mitogenic stimuli.Blood,2002,99:3838.3843.