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移植心肌样细胞对心肌梗死后功能性室壁瘤大鼠心功能的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第2期
页码:
197
栏目:
基础研究
出版日期:
2009-03-30

文章信息/Info

Title:
Effect of cardiomyocytes-like cells transplantation on cardiac function of rats with ventricular aneurysm after myocardial infarction
作者:
杜娟娟; 陶凌; 周祥; 张英梅; 邢玉洁; 王利; 赵晓梅; 吕安林
第四军医大学西京医院心血管内科，陕西 西安 710032
Author(s):
DU Juan-juan;  TAO Ling;  ZHOU Xiang;  ZHANG Ying-mei;  XING Yu-jie;  WANG Li;  ZHAO Xiao-mei;  L An-lin
Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
骨髓间充质干细胞; 心肌样细胞; 移植; 功能性室壁瘤
Keywords:
mesenchymal stem cells;  cardiomyocytes-like cells;  transplantation;  functional ventricular aneurysm
分类号:
R617
DOI:
-
文献标识码:
A
摘要:
目的 探讨心肌内注射心肌样细胞对心肌梗死(MI)后功能性室壁瘤大鼠心功能的影响。方法 结扎大鼠冠状动脉前降支形成MI，4周后,用超声心动图检测并筛选形成功能性室壁瘤者，并随机分为两组，即移植组（n=10），在室壁瘤部位及周边点状注射5-氮杂胞苷(5-Aza)诱导骨髓间充质干细胞（MSCs）分化、并用4,6-二脒基-2-苯基吲哚(DAPI)标记的心肌样细胞（106～107个）；对照组（n=10）：注射生理盐水。另取10只健康大鼠作为假手术组，只开胸不做任何处理。4周后，用超声心动图和血流动力学方法测定功能性室壁瘤大鼠的心功能，在荧光显微镜下观察DAPI标记的移植细胞的存活情况。结果 超声心动图的结果显示，对照组和移植组的左室舒张末内径（LVEDD）和左室收缩末内径（LVESD）均较假手术组增高（P<0.01），而移植组较对照组有所降低［（8.749±0.091）、（5.109±0.171） vs (9.219±0.059)mm、(5.942±0.092)mm,P<0.05］；对照组和移植组的短轴缩短率（△FS）及左室射血分数（LVEF）均较假手术组明显降低（P<0.01），移植组较对照组两者有所增高［（32.70±1.283）、（45.78±1.796） vs （22.80±0.593）%、（31.92±0.830）%，P<0.05］。血流动力学检测结果显示，移植组、对照组和假手术组的左室舒缩压差（LVDP）和左室正负最大变化速率（±dp/dtmax），分别为（152.9±0.669）、（4109±33.86）、（-3579±49.09），（122.5±2.639）、（3823±73.50）、（-2828±60.96）和（183.6±2.348）mmHg、（6 695±80.17）mmHg/s、（-6 294±71.39）mmHg/s，假手术组优于对照组和移植组（P<0.01），移植组优于对照组（P<0.05）。在荧光显微镜下可以观察到移植组的心肌组织中有存活的标记细胞。结论 移植心肌样细胞能显著改善MI后功能性室壁瘤大鼠的心功能，为治疗功能性室壁瘤提供一种新的治疗思路和为临床研究奠定基础。
Abstract:
AIM To observe the effect of cardiomyocytes-like cells induced from mesenchymal stem cells (MSCs）transplantation on the cardiac function of rats with functional ventricular aneurysm after myocardial infarction. METHODS Isolated MSCs from rats bone marrow were cultured in cell culture medium with 5-azacytidine (5-Aza) and labeled with 4,6-diamidino-2-phenylindole (DAPI）. Functional ventricular aneurysm model of rat was established by ligating the left enterior descending coronary artery and selected by ultrasonic cardiography (UCG) after 4 weeks. The rats with functional ventricular aneurysm were divided into cardiomyocytes-like cells group and control group then cardiomyocytes-like cells (106-107) or sodium chloride were injected at several different points into the broad area of ventricular aneurysm. In addition, 10 SD rats served as sham operation group (thoracotomy twice without ligation of coronary artery. Four weeks after transplantation, the cardiac function of the rats was measured by UCG and multichannel physiological recorder and the transplanted cardiomyocytes-like cells were detected by fluorescent microscope. RESULTS UCG showed that left ventricular end diastolic dimension (LVEDD) and left ventricular end systolic (LVESD) dimension in the three groups were （8.749±0.091）, （5.109±0.171）; (9.219±0.059), (5.942±0.092） and (6.344±0.296) mm, (3.116±0.275) mm, with sham operation group best（P<0.01） and cardiomyocytes-like cells group better than control group（P<0.05）. Fractional shortening (△FS) and left ventricular ejection fraction (LVEF) in the three groups were (32.70±1.283), (45.78±1.796); (22.80±0.593), (31.92±0.830) and (54.90±2.742)%, (74.12±2.760)%, with sham operation group highest（P<0.01） and cardiomyocytes-like cells group higher than control group（P<0.05）. Multichannel physiological recorder showed that left ventricular developed pressure (LVDP) and (±dp/dtmax) in the three groups were（152.9±0.669), (4 109±33.86), (-3 579±49.09); (122.5±2.639), (3 823±73.50), (-2 828±60.96) and (183.6±2.348) mmHg, (6 695±80.17) mmHg/s, (-6 294±71.39) mmHg/s, with sham operation group best（P<0.01） and cardiomyocytes-like cells group better than control group（P<0.05）. Labeled cardiomyocytes-like cells were found on the broad area of ventricular aneurysm in cardiomyocytes-like cells group. CONCLUSION Cardiomyocytes-like cells transplantation can improve the heart function of rat with functional ventricular aneurysm after myocardial infarction, provide a new therapeutic way and lay fundation for clinical reaserch.

参考文献/References

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备注/Memo

备注/Memo:
收稿日期：2008-11-25.通讯作者：吕安林，副主任医师，主要从事冠心病的介入治疗和组织工程的研究Email:lvanlin@fmmu.edu.cn 作者简介：杜娟娟，硕士生Email:dujuanjuanly@126.com
更新日期/Last Update: 2009-04-16