中国组织工程研究

中国组织工程研究 ›› 2011, Vol. 15 ›› Issue (45): 8474-8478.doi: 10.3969/j.issn.1673-8225.2011.45.025

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

血红素氧合酶1修饰骨髓间充质干细胞多点注射梗死灶周围对梗死后心肌结构重塑的影响

张  静，黎明江，曾  彬   

  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:2011-08-07 修回日期:2011-10-05 出版日期:2011-11-05 发布日期:2011-11-05
  • 通讯作者: 黎明江，博士，教授，主任医师，武汉大学人民医院心血管内科，湖北省武汉市 430060 mingjiangLi@yahoo.com.cn
  • 作者简介:张静★，女，1986年生，河南省南阳市人，汉族，在读硕士，主要从事心血管疾病的研究。 zxquzj@163.com
  • 基金资助:

    国家自然科学基金青年基金(30900609)。

Effects of multiple injection of bone marrow mesenchymal stem cells modified with heme oxygenase 1 on myocardial remodeling after myocardial infarction

Zhang Jing, Li Ming-jiang, Zeng Bin   

  1. Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan  430060, Hubei Province, China
  • Received:2011-08-07 Revised:2011-10-05 Online:2011-11-05 Published:2011-11-05
  • Contact: Li Ming-jiang, Doctor, Professor, Chief physician, Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China mingjiangLi@yahoo.com.cn
  • About author:Zhang Jing★, Studying for master’s degree, Department of Cardiovascular Disease, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, China
  • Supported by:

    Young Scientists Fund of National Natural Science Foundation of China, No. 30900609*

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277

被引次数

2

摘要：

背景：研究表明血红素氧合酶1的过表达有抗炎症反应的作用，将血红素氧合酶1修饰的骨髓间充质干细胞(HO-1-BMSCs)移植入梗死心脏周围是否可调节基质金属蛋白酶/组织金属蛋白酶抑制剂的比例而明显改善梗死心肌重构呢？
目的：观察血红素氧合酶1修饰的骨髓间充质干细胞移植对心肌梗死后心肌胶原的调节及心肌重塑的逆转作用。
方法：利用血红素氧合酶1腺病毒转染体外培养扩增的骨髓间充质干细胞。结扎大鼠左前降支动脉制造心肌梗死模型，1 h后，分别将HO-1-BMSCs、BMSCs多点注射到大鼠心脏梗死区四周，对照组注射等量磷酸盐缓冲液。
结果与结论：Adv-hHO-1转染BMSCs后获稳定表达；hHO-1-mRNA仅在HO-1-BMSCs移植组表达；与对照组相比，HO-1-BMSCs移植组基质金属蛋白酶2/9的表达显著减少(P < 0.05)，Null-BMSCs组基质金属蛋白酶2/9的表达虽然减少，但差异无显著性意义(P > 0.05)；与对照组相比，细胞移植组金属蛋白酶组织抑制剂2/3的表达显著增加，尤以HO-1-BMSCs组明显(P < 0.05)；但金属蛋白酶组织抑制剂1无明显变化(P > 0.05)。金属蛋白酶组织抑制剂2/基质金属蛋白酶2和金属蛋白酶组织抑制剂3/基质金属蛋白酶9的比例在细胞移植的心脏中明显上升。与对照组比较，细胞移植组心室中的胶原蛋白沉积减少，心室腔内径显著缩小。结果表明血红素氧合酶1修饰的骨髓间充质干细胞移植可使基质金属蛋白酶/组织金属蛋白酶抑制剂的比例正常化，并逆转心肌细胞外基质的重构。

关键词: 血红素氧合酶1, 骨髓间充质干细胞, 心肌梗死, 基质金属蛋白酶2/9, 组织金属蛋白酶抑制剂1/2/3

Abstract:

BACKGROUND: Studies have shown that over-expression of heme oxygenase 1 (HO-1) has the effect of anti-inflammation. It is unclear whether injection of bone marrow mesenchymal stem cells (BMSCs) modified with heme oxygenase-1 (HO-1-BMSCs) in infarcted myocardium can significantly improve myocardial remodeling by regulating the ratio of matrix metalloproteinase (MMP) to tissue inhibitors of metalloproteinase (TIMP).
OBJECTIVE: To investigate the effects of transplantation of HO-1-BMSCs on regulating collagens and myocardial remodeling after myocardial infarction.
METHODS: BMSCs were cultured and amplificated with HO-1 adenovirus (Adv-HO-1) transfection in vitro. Myocardial infarction models in rats were established by ligating the left anterior descending coronary artery. One hour after modeling, HO-1-BMSCs and BMSCs were respectively transplanted into the infarcted myocardium of rats in a manner of multiple injections. The rats in the control group were given phosphate buffer in the same dose.
RESULTS AND CONCLUSION: Adv-HO-l stably expressed in BMSCs after transfection, while hHO-1-mRNA only expressed in HO-1-BMSCs. The expression of MMP2/9 in the HO-1-BMSCs group was decreased compared with that in the control group (P < 0.05), the reduction in Null- BMSCs was insignificant (P > 0.05). Compared with the control group, the expression of MMP2/3 was significantly increased in the other two groups, especially in the HO-1-BMSCs group (P < 0.05), but MMP1 did not change significantly (P > 0.05). The ratio of TIMP2 to MMP2 in cell transplantation groups was significantly increased, so was the ratio of TIMP3 to MMP9. Collagen was deposition decreased and ventricular was reduced in cell transplantation groups compared with the control group. The results showed that injection of HO-1-BMSCs can normalize the ratio of MMPs/TIMPs, as well as contribute to the revision of myocardial extracelluar remodeling.

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