人脐血干细胞移植对心肌梗死大鼠血管新生和血管内皮生长因子、促血管生成素-1表达的影响Effects of transplantation of human umbilical cord blood stem cells on angiogenesis and expression of vascular endothelial growth factor and angiopoietn-1 in rats with experimental myocardial infarction
赵林,王雷,贾三庆,张宇晨,李贵华,李虹伟,顾复生
摘要(Abstract)：
目的观察人脐血干细胞(hUCBSC)经静脉移植对心肌梗死(MI)大鼠血管新生和血管内皮生长因子(VEGF)、促血管生成素(Ang-1)表达的影响。方法雄性Sprague-Dawley大鼠40只,随机分为3组:(1)假手术组(10只):大鼠麻醉后开胸,将结扎线通过前降支动脉(LAD),不结扎,然后关胸;(2)对照组(15只):大鼠麻醉后开胸,结扎LAD,制备MI模型成功(经肉眼观察和心电图证实)后,经尾静脉注射0.9%生理盐水0.5 mL;(3)移植组(15只),大鼠麻醉后开胸,结扎LAD,制备MI模型后,经尾静脉注射hUCBSC 0.5 mL(含干细胞2×107/mL,由北京市脐血干细胞库提供)。术后4周行超声心动图检查和心导管检查,并取心脏组织行HE染色、抗Ⅷ因子免疫组化染色,观察心肌病理改变、肌毛细血管密度(MCD)的变化。同时用免疫组化和RT-PCT的方法检测VEGF、Ang-1及其mRNA的表达。结果与对照组相比,术后4周时移植组左室射血分数较对照组明显改善(55.35%±11.23%比40.23%±10.87%,P<0.01),左室舒张末压显著降低(10.56±4.69 mmHg比20.13±5.63 mmHg,P<0.01),而左室压力最大变化率明显增加(4.25±2.01 mmHg比6.53±2.38mmHg,P<0.05;3.83±2.69 mmHg比6.25±2.92 mmHg,P<0.05);移植组MCD明显高于对照组(每高倍视野4.2±0.5个比2.1±0.3个,P<0.01);移植组VEGF和Ang-1及其mRNA表达明显高于对照组和假手术组。结论经静脉移植hUCBSC促进MI大鼠VEGF和Ang-1表达,促进血管新生,改善心功能。
关键词(KeyWords)： 脐血干细胞移植;心肌梗死;新生血管化,病理性;血管内皮生长因子类;促血管生成素-1
基金项目(Foundation):
作者(Author): 赵林,王雷,贾三庆,张宇晨,李贵华,李虹伟,顾复生
参考文献(References)：
- [1]Orlic D,Kajstura J,Chimenti S,et al.Bone marrowcells regen-erate infracted myocardium.Nature,2001,410:701-705.
- [2]Dohmann HF,Perin EC,Takiya CM,et al.Transendocardialautologous bone marrow mononuclear cell injection in ischemicheart failure:postmortem anatomicopathologic and immunohisto-chemical findings.Circulation,2005,112:521-526.
- [3]Jain M,DerSimonian H,Brenner DA,et al.Cell therapy attenu-ates deleterious ventricular remodeling and improves cardiac per-formance after myocardial infarction.Circulation,2001,103:1920-1927.
- [4]Ma N,Stamm C,Kaminski A,et al.Human cord blood cells in-duce angiogenesis following myocardial infarction in NOD/scid-mice.Cardiovasc Res,2005,66:45-54.
- [5]Hirata Y,Sata M,Motomura N,et al.Human umbilical cordblood cells improve cardiac function after myocardial infarction.Biochem Biophys Res Commun,2005,327:609-614.
- [6]Leor J,Guetta E,Feinberg MS,et al.Human umbilical cordblood-derived CD133+cells enhance function and repair of theinfracted myocardium.Stem Cells,2006,24:772-780.
- [7]胡承恒,伍富贵,王小庆,等.人脐血单个核细胞移植治疗大鼠急性心肌梗死的实验研究.中华心血管病杂志,2006,34:587-590.
- [8]Kim BO,Tian H,Prasongsukarn K,et al.Cell transplantationimproves ventricular function after a myocardial infarction:a pre-clinical study of human unrestricted somatic stem cells in a por-cine model.Circulation,2005,112:I96-104.
- [9]Pomyje J,Zivny J,Sefc L,et al.Expression of genes regulatingangiogenesis in human circulating hematopoietic cord bloodCD34+/CD133+cells.Eur J Haematol,2003,70:143-150.
- [10]刘翔,陈亦江,张馥敏,等.VEGF165和Ang-1协同改善急性心梗大鼠心功能.中华胸心血管外科杂志,2005,21:295-297.