自体外周血内皮祖细胞移植对小型猪心肌缺血再灌注损伤的作用Effect of autologous transplantation of peripheral endothelial progenitor cells on myocardial ischemia reperfusion injury in mini-swine
李崇剑,高润霖,杨跃进,胡奉环,杨伟宪,宋来凤,阮英茆,乔树宾,陈纪林,秦学文,陈在嘉
摘要(Abstract)：
目的研究自体外周血内皮祖细胞(EPCs)移植对小型猪心肌缺血再灌注损伤后修复梗死心肌和改善心功能的作用。方法14头小型猪分别采外周血200 mL用于EPCs分离、培养,10~14 d后结扎法建立心肌缺血再灌注损伤模型,随机分为冠状动脉内移植EPCs组[(1.16±1.07)×107个细胞/头,n=7]和磷酸盐缓冲液对照组(n=7),比较4周时超声心动图、血液动力学和心肌梗死面积的变化。结果移植4周后,EPCs组左室射血分数(LVEF),室间隔、侧壁、前间壁厚度,心输出量和左室等容收缩压力最大上升速率(+dp/dtmax)与细胞移植前比较,差异均无统计学意义(P>0.05);对照组比移植前LVEF显著降低(0.59±0.07比0.70±0.09),室间隔(0.56±0.05 cm比0.66±0.06 cm)、侧壁(0.52±0.09 cm比0.62±0.05 cm)、前间壁(0.51±0.12 cm比0.70±0.14 cm)显著变薄,心输出量(1.10±0.08 L/min比1.27±0.03 L/min)和+dp/dtmax[(1.41±0.22)×103mmHg/s比(1.76±0.31)×103mmHg/s]显著降低,差异均有统计学意义(P<0.05);EPCs组较对照组心肌梗死面积显著减小(1.60±0.26 cm2比4.14±1.30 cm2,P<0.05)。结论自体EPCs移植可明显改善心肌缺血再灌注损伤后的左室收缩功能,该作用可能通过减小心肌梗死面积实现。
关键词(KeyWords)： 心肌再灌注损伤;心肌梗死;外周血干细胞移植;猪,雏型
基金项目(Foundation):
作者(Author): 李崇剑,高润霖,杨跃进,胡奉环,杨伟宪,宋来凤,阮英茆,乔树宾,陈纪林,秦学文,陈在嘉
参考文献(References)：
- [1]Assmus B,Schachinger V,Teupe C,et al.Transplantation ofprogenitor cells and regeneration enhancement in acute myocardi-al infarction(TOPCARE-AMI).Circulation,2002,106:3009-3017.
- [2]Ichioka S,Kudo S,Shibata M,et al.Bone marrowcell Implan-tation improves flap viability after ischemia-reperfusion injury.Ann Plast Surg,2004,52:414-418.
- [3]McDonald DM,Teicher BA,Stevenson WS,et al.Report fromthe society for biological therapy and vascular biology faculty ofthe NCI workshop on angiogenesis monitoring.J Immunother,2004,27:161-175.
- [4]李崇剑,高润霖,宋来凤,等.用结扎法建立小型猪心肌缺血再灌注模型损伤模型.中国分子心脏病杂志,2006,6:30-32.
- [5]李崇剑,高润霖,刘玉清,等.小型猪外周血内皮祖细胞的体外培养与分化研究.中国病理生理杂志,2005,21:1230-1233.
- [6]Wollert KC,Drexler H.Clinical applications of stem cells for theheart.Circ Res,2005,96:151-163.
- [7]Strauer BE,Brehm M,Zeus T,et al.Repair of infarcted myo-cardium by autologous intracoronary mononuclear bone marrowcell transplantation in humans.Circulation,2002,106:1913-1918.
- [8]Kamihata H,Matsubara H,Nishiue T,et al.Implantation ofbone marrow mononuclear cells into ischemic myocardium en-hances collateral perfusion and regional function via side supply ofangioblasts,angiogenic ligands,and cytokines.Circulation,2001,104:1046-1052.
- [9]Fernandez-Aviles F,Roman JAS,Garcia-Frade J,et al.Experi-mental and clinical regenerative capability of human bone marrowcells after myocardial infarction.Circ Res,2004,95:742-748.
- [10]Orlic D,Kajstura J,Chimenti S,et al.Bone marrowcells regen-erate infarcted myocardium.Nature,2001,410:701-705.
- [11]Alvarez-Dolado M,Pardal R,Garca-Verdugo JM,et al.Fusionof bone marrow-derived cells with Purkinje neurons,cardiomyo-cytes and hepatocytes.Nature,2003,425:968-973.
- [12]Nygren JM,Jovinge S,Breitbach M,et al.Bone marrow-derivedhematopoietic cells generate cardiomyocytes at a low frequencythrough cell fusion,but not transdifferentiation.Nat Med,2004,10:494-501.
- [13]Goodell MA.Stem-cell"plasticity":befuddled by the muddle.Curr Opin Hematol,2003,10:208-213.
- [14]He T,Peterson TE,Holmuhamedov EL,et al.Human endothe-lial progenitor cells tolerate oxidative stress due to intrinsicallyhigh expression of manganese superoxide dismutase.ArteriosclerThromb Vasc Biol,2004,24:2021-2027.
- [15]Rossig L,Urbich C,Dimmeler S.Endothelial progenitor cells atwork:not mature yet,but already stress-resistant.ArteriosclerThromb Vase Biol,2004,24:1977-1979.