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心肌、冠脉、静脉内移植BM-MNCs治疗猪急性心肌梗死的时机及安全性

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2010年第5期
页码:
658-663
栏目:
基础研究
出版日期:
2010-06-22

文章信息/Info

Title:
Optimal time and safety of intramyocardial, intracoronary or intravenous transplantation of autologous bone-marrow-derived mononuclear cells into ischemic myocardium of AMI in swine
作者:
孙林1张戈1左明鲜2周旭1章体玲2白文伟1杨达宽1
1.昆明医学院第二附属医院心血管内科,云南省冠心病基础研究室,云南 昆明 650101;2.昆明市延安医院心血管内科, 云南 昆明 650051
Author(s):
SUN Lin ZHANG Ge ZUO Ming-xian ZHOU Xu ZHANG Ti-ling BAI Wen-wei YANG Da-kuan
Department of Cardiology, Second Affiliated Hospital, Kunming Medical College, Kunming 650101, Yunnan, China
关键词:
骨髓单个核细胞移植急性心肌梗死
Keywords:
bone-marrow-derived mononuclear cells transplantation acute myocardial infarction swine
分类号:
R392.4
DOI:
-
文献标识码:
A
摘要:
目的: 探讨心肌内、冠脉内及静脉内3种途径移植自体骨髓单个核细胞(BM-MNCs)治疗猪急性心肌梗死的时机及安全性。方法: 分别于心肌梗死(MI)后即刻进行心肌内及静脉内移植,于MI后1周进行冠脉内移植。移植BM-MNCs后4周,观察小血管密度、心功能变化及冠脉侧支循环形成的情况,探讨移植的时机及安全性。结果: ①3种途径BM-MNCs移植后4周,小血管的密度均明显高于各自的对照(P<0.01);心肌内移植与冠脉内移植相比,小血管的密度无统计学差异,但明显高于静脉内移植(P<0.01)。②3种途径移植BM-MNCs后4周,左室射血分数(LVEF)和缩短分数(FS)组相比较无统计学差异。心肌内移植和冠脉内移植的左室舒张末压(LVDEP)和左室舒张末期内径(LVEDD)均明显低于对照;而静脉内移植的LVDEP和LVEDD虽低于对照但无统计学差异。③3种途径移植BM-MNCs后1周,血清碱性成纤维细胞生长因子(bFGF)及血管内皮生长因子(VEGF)的浓度明显高于各自对照及术前水平(P<0.01)。④3种途径移植BM-MNCs后,均没有发现异常增生、钙化或肿瘤形成。结论: ①心肌内及静脉内移植的时机应选在MI后即刻,冠脉内移植的时机应选在MI后1周。3种途径移植BM-MNCs后,均有助于促进缺血心肌中的血管新生,改善左室收缩功能。心肌内与冠脉内移植BM-MNCs均有改善左室舒张功能、减轻心室重构的作用,但在静脉内移植后该作用不明显。②3种途径移植BM-MNCs后,均没有发现明显的副作用。
Abstract:
AIM: To study the optimal time and safety of intramyocardial, intracoronary or intravenous (i.v.) transplantation of autologous bone-marrow-derived mononuclear cells (BM-MNCs) into ischemic myocardium of acute myocardial infarction (AMI) in swine. METHODS: Transplantation was performed immediately after myocardial infarction in intramyocardial group and i.v. group, whereas transplantation was performed 1 week after myocardial infarction in intracoronary group. Four weeks later, blood vessel density, heart function, collateral circulation formation and side effects were observed and compared. RESULTS: Blood vessel density in the three BM-MNCs transplantation groups was significantly higher than in their respective control group (P<0.01). No significant difference was observed in blood vessel density between intramyocardial group and intracoronary group but blood vessel density in intramyocardial group was significantly higher than in i.v. group (P<0.01). No significant difference was found in left ventricular ejection fraction (LVEF) and fraction shortening of short axis (FS) among the three transplantation groups. Left ventricular end-diastolic pressure (LVDEP) and left ventricular end-diastolic dimension (LVEDd) in intramyocardial group and intracoronary group were lower than in control group, but no significance was observed between i.v. group and control group. One week after transplantation, the levels of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) in the three transplantation group were significantly higher than those in control group and before operation (P<0.01). No side effects such as abnormal angiogenesis, calcification or cancer were observed in the three transplantation groups. CONCLUSIONS: No obvious side effects are observed in intramyocardial, intracoronary or i.v. transplantation of BM-MNCs into myocardium of AMI in swine. The optimal time for intramyocardial or i.v. transplantation is immediately after myocardial infarction and the optimal time for intracoronary transplantation is 1 week after myocardial infarction. Intramyocardial, intracoronary or i.v. transplantation all induces angiogenesis in the ischemic myocardium and improves left ventricular systolic function. The therapeutic efficacy of intramyocardial or intracoronary transplantation is similar but better than the efficacy of i.v. transplantation. Intramyocardial and intracoronary transplantation improves left ventricular diastolic function and attenuates remodeling but these effects are not as effective in i.v. transplantation.

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备注/Memo

备注/Memo:
收稿日期:2009-08-28.通讯作者:孙林,副教授,主要从事冠心病基础及临床研究Email:sunlinkm@sina.com.cn
更新日期/Last Update: 2010-06-22