心肌梗死后不同移植部位对移植后骨髓间充质干细胞的影响

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摘要目的：探讨在心肌梗死（MI）后不同的细胞移植部位是否会对植入细胞的存活以及心功能的改善程度产生影响。方法：利用结扎雌性大鼠冠状动脉前降支的方法来制作大鼠MI模型，3周后将3×106个5-溴尿嘧啶（Brdu）标记的雄性大鼠来源的骨髓间充质干细胞（BMSCs）利用注射的方法分别移植于雌性大鼠MI的边缘区（BZC组）和中央区（CZC组）；在对照组中用相同体积的PBS分别注射于MI边缘区（BZP组）和中央区部位（CZP组）。分别在移植后的24 h和4周利用实时定量RT-PCR检测Y染色体性别决定区（SRY）基因来观测移植细胞的存活量，在4周后利用心脏超声来评估心功能情况。处死大鼠后用HE染色法检测MI区的瘢痕厚度和心脏的膨胀系数，利用VIII因子免疫组织化学法检测移植的BMSCs的促血管新生作用。结果：在细胞移植后的24 h和4周的细胞存活率检测中BZC组均显著高于CZC组，差异均有统计学意义（P＜0.01）。并且在心超检测结果中BZC组的左室射血分数（LVEF）与左室缩短分数（LVFS）均较CZC组有显著提高，差异有统计学意义（P＜0.05）。血管增生检测中BZC组亦明显优于CZC组，差异有统计学意义（P＜0.01）。在心室形态学重塑检测中BZC组的膨胀系数较CZC组显著降低，差异有统计学意义（P＜0.01）。而在瘢痕厚度的检测中，BZC组和CZC组均显著高于对照组，差异有统计学意义（P＜0.01）。结论：MI边缘区移植更有利于移植细胞的存活，继而能进一步促进血管新生和改善心功能。

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	金培峰
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	孙成超

关键词 ：间充质干细胞, 心肌梗死, 细胞移植, 心室重构, 大鼠

Abstract：Objective: To determine whether the injection sites of myocardial infarcted area had a various effect on the bone marrow mesenchymal stem cells (BMSCs) survival and efficacy of cell transplantation. Methods: Myocardial infarction (MI) was induced by left anterior descending artery ligation in female rats. 3 weeks after MI, 3×106 bromodeoxyuridine (Brdu) labeled male BMSCs were directly intramyocardial injected into the borderline (BZC group) or central zone (CZC group) of the MI area. In the control groups, the same volume of phosphate buffered saline (PBS) was injected into the borderline (BZP) or the central zone of the myocardial infarction (CZP), respectively. Cell survival at the 24 hours and 4 weeks after transplantation was assayed by quantitative real-time PCR to identify Y chromosome gene. Heart function was evaluated by echocardiography before and after cell transplantation. Ventricular remodeling was analysis by using HE staining with measurement of the expansion index and scar thickness. Cell transplantation induced angiogenesis was tested by VIII factor staining. Results: The detectable transplanted cell survival rate in the BZC group were significantly higher than that of CZC group both at the time of 24 h (15.74%±4.13% vs. 8.2%±2.63%, P<0.01) and 4 weeks (5.57%±1.13% vs. 1.72%±0.41%, P<0.01) after cell transplantation. Compared with the CZC group, improvement of left ventricular ejection fraction (LVEF) and fractional shortening (P<0.05, respectively) were observed in BZC group. Additionally, BMSCs transplanted in the borderline zone also induced augmentation of capillary density than that in the CZC group (P<0.01). Left ventricular remodeling (scar thickness expansion index) in BZC group was significantly improved (P<0.01), and no improved expansion index was identified in CZC group. Conclusion: Borderline area was more suitable than central zone of MI for the survival of the transplanted cells and thereby promoted the angiogenesis and restored the damaged heart function.

Key words： mesenchymal stem cells myocardial infarction cell transplantation ventricular remodeling rats

收稿日期: 2017-10-17

基金资助:国家自然科学基金青年基金资助项目（81500220）；温州市科技计划项目（Y20150072）。

通讯作者: 孙成超，教授，主任医师，硕士生导师，Email：suncc6@163.com

作者简介: 金培峰（1984-），男，浙江乐清人，主治医师，硕士。

链接本文:

https://xb.wmu.edu.cn/CN/ 或 https://xb.wmu.edu.cn/CN/Y2018/V48/I7/485

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