小型猪自体骨髓单个核细胞移植对心肌梗死后心室重构的影响Effects of autologous transplantation of bone marrow mononuclear cells on ventricular remodeling after myocardial infarction in swines
徐晓蓉,温尚煜,郭艳红,李昭屏,潘震华,毛节明,周春燕,高炜
摘要(Abstract):
目的观察小型猪自体骨髓单个核细胞移植对改善心肌梗死后心室重构的影响并探讨可能的机制。方法采用经冠状动脉球囊堵闭法制作小型猪前壁心肌梗死动物模型,喂养3周后随机分为经皮冠状动脉内骨髓单个核细胞(BM-MNC)移植组(n=7)和磷酸盐缓冲液(PBS)对照组(n=5)。BM-MNC移植组注入BM-MNC悬液10mL至梗死相关血管,对照组注入PBS10mL至梗死相关血管。继续喂养4周后采用超声心动图、左心室造影评价心脏结构和功能,用羟脯氨酸消化法测定心肌胶原含量,以天狼猩红染色后观察胶原纤维形态。结果移植后4周BM-MNC移植组左心室舒张末内径(LVEDD)较移植前缩小(40.40±4.51mm比45.88±4.15mm,P=0.026),左心室射血分数(LVEF)较移植前增加(47.50%±9.07%比41.16%±9.83%,P=0.020);对照组LVEDD较移植前有所增加(48.50±9.31mm比42.40±7.29mm,P=0.328),射血分数无明显变化。两组移植前后LVEDD及LVEF的差值比较,差异均有统计学意义(-5.48±0.71mm比6.10±1.39mm,P=0.046;5.33%±2.88%比0.20%±1.38%,P=0.030)。BM-MNC移植组在交界区及远离区胶原含量均较对照组减少(1.32±0.49μg/mg比0.71±0.35μg/mg,P=0.047;0.32±0.05μg/mg比0.21±0.08μg/mg,P=0.034),胶原排列整齐;梗死区胶原含量和形态两组无明显差异。结论BM-MNC移植治疗可改善心肌梗死后心室重构过程,心肌胶原含量的减少可能是其重要的机制之一。
关键词(KeyWords): 骨髓细胞;心肌梗死;心室重构;干细胞移植
基金项目(Foundation): “十五”国家科技攻关计划项目(2004BA714B-1)
作者(Author): 徐晓蓉,温尚煜,郭艳红,李昭屏,潘震华,毛节明,周春燕,高炜
参考文献(References):
- [1]Jain M,Simonian H,Brenner DA,et al.Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction.Circulation,2001,103:1920-1927.
- [2]Britten MB,Abolmaali ND,Assmus B,et al.Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction(TOPCARE-AMI):mechanistic insights from serial contrast-enhanced MRI.Circulation,2003,108:2212-2218.
- [3]Fuchs S,Baffour R,Zhou YF,et al.Transendocardial delivery of autologous bone marrow enhances collateral perfusion and regional function in pigs with chronic experimental myocardial ischemia.J Am Coll Cardiol,2001,37:1726-1733.
- [4]Lin GS,Lu JJ,Jiang XJ,et al.Autologous transplantation of bone marrow mononuclear cells improved heart function after myocardial infarction.Pharmacol Sin,2004,25:876-886.
- [5]Tomita S,Mickle DA,Weisel RD,et al.Improved heart function with myo-genesis and angiogenesis after autologous porine bone marrow stromal cell transplantation.J Thorac Cardiovasc Surg,2002,123:1132-1140.
- [6]Gerd P,Meyer MD,Kai C,et al.Intracoronary bone marrow cell transfer after myocardial infarction eighteen months'follow-up data from the randomized,controlled Boost trial.Circulation,2006,113:1287-1294.
- [7]孙晓楠,刘国树,石蕊,等.骨髓间质干细胞移植对自发性高血压大鼠心脏纤维化及心功能的影响.高血压杂志,2005,13:109-113.
- [8]Zhang SH,Guo JX,Zhang P,et al.Long-term effects of bone marrow mononuclear cell transplantation on left ventricular function and remodeling in rats.Life Sciences,2004,74:2853-2864.
- [9]Shake JG,Gruber PJ,Baumgartner WA,et al.Mesenchymal stem cell implantation in a swine myocardial infarct model:engraftment and functional effects.Ann Tho rac Surg,2002,73:1919-1925.
- [10]Lovelock JD,Baker AH,Gao F,et al.Heterogeneous effects of tissue inhibitors of matrix metalloproteinases on cardiac fibroblasts.Am J Physiol Heart Circ Physiol,2005,288:H461.
- [11]Xu X,Xu Z,Xu Y,et al.Selective down-regulation of extracelluar matrix gene expression by bone marrow drived stem cell transplantation into infarcted myocardium.Circ J,2005,69:1275-1283.