中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (40): 7416-7420.doi: 10.3969/j.issn.1673-8225.2011.40.002

• 骨髓干细胞 bone marrow stem cells • 上一篇    下一篇

血红素氧合酶1提高骨髓间充质干细胞在梗死后心脏的存活

曾  彬,易  欣,马乐乐   

  1. 武汉大学人民医院心血管内科,湖北省武汉市430060
  • 收稿日期:2011-04-12 修回日期:2011-08-16 出版日期:2011-10-01 发布日期:2011-10-01
  • 作者简介:曾彬☆,男,1978年生,湖北省黄石市人,汉族,2008年武汉大学毕业,博士,主治医师,主要从事冠心病基础与临床的研究。 zengbinwhu@yahoo.com
  • 基金资助:

    国家自然科学基金资助项目(30900609)。

Human heme oxygenase-1 improves the survival of bone marrow mesenchymal stem cells in ischemic heart

Zeng Bin, Yi Xin, Ma Le-le   

  1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan  430060, Hubei Province, China
  • Received:2011-04-12 Revised:2011-08-16 Online:2011-10-01 Published:2011-10-01
  • About author:Zeng Bin☆, Doctor, Attending physician, Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China zengbinwhu@yahoo.com
  • Supported by:

    the National Natural Science Foundation of China, No. 30900609*

摘要:

背景:移植骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)修复梗死后心功能受到围移植期移植细胞大量死亡的限制。因此寻找一种保护因子对移植细胞提供保护至关重要。
目的:观察血红素氧合酶1(heme oxygenase,HO-1)对BMSCs在梗死后心脏生存的影响。
方法:体外分离扩增培养大鼠BMSCs,Adv-hHO-1、Adv-GFP分别转染,移植前DAPI标记。结扎左前降支1 h后,分别将DAPI-hHO-1-BMSCs、DAPI-GFP-BMSCs多点注射到大鼠心脏梗死区周边,对照组注射等量PBS。
结果与结论:Adv-hHO-1转染BMSCs后获稳定表达。仅hHO-1-BMSCs组稳定表达hHO-1 mRNA;hHO-1-BMSCs组血管内皮生长因子、碱性成纤维细胞生长因子、肝细胞生长因子表达均高于其他两组(P < 0.01);存活BMSCs数量在第3,7天均明显高于GFP-BMSCs组(P < 0.05);大鼠心功能各项参数明显优于其他两组(P < 0.01)。移植4周后,HO-1-BMSCs组梗死区周边毛细血管密度明显高于GFP-BMSCs组和对照组(P < 0.01),且胶原蛋白沉积减少,心室壁变厚,梗死面积较其他两组明显缩小(P < 0.01)。提示HO-1提高移植到梗死心脏BMSCs的存活,HO-1协同BMSCs抑制心室重构,改善心功能。

关键词: 血红素氧合酶1, 骨髓间充质干细胞, 心肌梗死, 细胞因子, 血管新生

Abstract:

BACKGROUND: Cardiac function is limited by the great amount of dead transplanted cells following myocardial infarction (AMI) treatment with bone marrow mesenchymal stem cells (BMSCs) transplantation.
OBJECTIVE: To investigate the effects of human heme oxygenase-1 (HO-1) on the survival of BMSCs in the heart after AMI.
METHODS: BMSCs were isolated, cultured and proliferated in vitro, transfected with Adv-hHO-1 and Adv-GFP, and then labeled with DAPI before transplantation. At 1 hour after left coronary artery ligation, DAPI-HO-1-BMSCs or DAPI-GFP-BMSCs were directly injected into the border of infracted cardiac region in rats. An equal volume of PBS was injected into the control group.
RESULTS AND CONCLUSION: The expression of hHO-1 mRNA, vascular endothelial growth factor, basic fibroblast growth factor, hepatocyte growth factor in the border of infracted cardiac region treated with HO-1-BMSCs were higher than those treated with GFP-BMSCs and PBS (P < 0.01), and the number of BMSCs and capillary vessels in AMI heart treated with HO-1-BMSCs was significantly higher than those treated with GFP-BMSCs and PBS (P < 0.05, P < 0.01). The heart function and remolding of the hearts treated with HO-1-BMSCs was better than those treated with GFP-BMSCs and PBS (P < 0.01). The infarct area in the HO-1-BMSCs group was also smaller than that in the GFP-BMSCs and PBS groups (P < 0.01). HO-1 enhances the survival of BMSCs in the AMI heart, which cooperates with BMSCs to inhibit ventricular remodeling and improve the cardiac function.

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