中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (27): 5010-5014.doi: 10.3969/j.issn.1673-8225.2010.27.016

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

静脉移植人脐血单个核细胞与心肌梗死家兔心肌细胞凋亡及凋亡基因bcl-2、bax

汪  弢，余国龙，周  波，潘  玮，卿丽琼   

  1. 中南大学湘雅医院心内科，湖南省长沙市  410008
  • 出版日期:2010-07-02 发布日期:2010-07-02
  • 通讯作者: 余国龙，教授，留美归国博士后，硕士研究生导师，中南大学湘雅医院心内科，湖南省长沙市 410008 yuguolong123@yahoo.com.cn
  • 作者简介:汪 弢★，男，1984年生，江苏省南通市人，中南大学在读硕士，医师，主要从事冠心病防治基础与临床研究。现在江苏省南通市第一人民医院心内科工作。 wangtao19840706@163.com

Effects of intravenous administration of human umbilical cord blood mononuclear cells on cardiomyocyte apoptosis and apoptosis genes bcl-2 and bax in rabbits after myocardial infarction  

Wang Tao, Yu Guo-long, Zhou Bo, Pan Wei, Qing Li-qiong   

  1. Department of Cardiology, Xiangya Hospital, Central Southern University, Changsha   410008, Hunan Province, China
  • Online:2010-07-02 Published:2010-07-02
  • Contact: Yu Guo-long, Professor, Doctor, Master’s supervisor, Department of Cardiology, Xiangya Hospital, Central Southern University, Changsha 410008, Hunan Province, China yuguolong123@yahoo.com.cn
  • About author:Wang Tao★, Studying for master’s degree, Physician, Department of Cardiology, Xiangya Hospital, Central Southern University, Changsha 410008, Hunan Province, China wangtao19840706@163.com

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370

被引次数

2

摘要：

背景：研究表明经冠状动脉或经心肌内脐血干细胞移植可促进心肌梗死区血管新生、减低心肌梗死范围和改善心功能等，但脐血干细胞静脉移植对心肌细胞凋亡的影响尚不清楚。
目的：观察人脐血单个核细胞静脉移植对急性心肌梗死心肌细胞凋亡及凋亡基因Bcl-2、Bax蛋白表达的影响。
方法：45只成年家兔随机分3组：移植组15只，于急性心肌梗死后24 h，经耳缘静脉注入2×107 BrdU标记人脐血单个核细胞悬液 500 μL；对照组15只，于急性心肌梗死后24 h，同途径注入生理盐水500 μL；假手术组15只，左前降支穿线不结扎，术后24 h同途径注入生理盐水500 μL。移植后1，2，4周超声检测心功能；移植后4周心肌组织切片苏木精-伊红染色观测心肌病理变化；脱氧核糖核酸末端转移酶介导末端标记法(TUNEL)检测心肌细胞凋亡；免疫组化法检测心肌BrdU阳性细胞及Bcl-2、Bax蛋白在心肌细胞表达水平。
结果与结论： ①与对照组比较，移植组心功能显著改善。②移植组梗死周边区存在BrdU阳性细胞。③与对照组比较，移植组Bcl-2蛋白水平显著升高，Bax蛋白水平显著降低。④移植术后4周移植组心肌细胞凋亡数显著低于对照组。实验证实经静脉移植人脐血单个核细胞可迁移至急性心肌梗死周边区；调控急性心肌梗死后心肌细胞Bcl-2及Bax蛋白表达水平，抑制梗死周边区域心肌细胞凋亡，并改善心肌梗死后心功能。

关键词: 心肌梗死, 脐血单个核细胞, 移植, 细胞凋亡, Bcl-2蛋白, Bax蛋白

Abstract:

BACKGROUND: The previous studies showed that intra-coronary or intra-myocadial intransplantation of human umbilical cord blood mononuclear cells (HUCBC) could promote angiogenesis, and reduce myocardial infarcted area associated with improvement of cardiac function. But, there is no study about the effect of human umbilical cord blood cells on cardiomyocyte apoptosis.
OBJECTIVE: To observe the effects of intravenous administration of HUCBC on cardiomyocyte apoptosis and the expressions of Bcl-2 and Bax proteins after acute myocardial infarction (AMI).
METHODS：A total of 45 adult rabbits were divided into three groups randomly: transplantation group with 15 rabbits was intravenously administrated with 500 μL HUCBC labeled with 2×107 bromodexyuridine (BrdU) at 24 hours after AMI: control group with 15 rabbits was intravenously administrated with 500 μL saline at 24 hours after AMI；sham operation group with 15 rabbits, not receiving ligation of left anterior descending branch, was intravenously administrated with 500 μL saline at 24 hours after operation. Cardiac functions were performed by echocardiography at 1, 2 and 4 weeks after transplantation. Myocardial tissue sections were observed using hematoxylin-eosin staining to measure pathological changes in myocardium at 4 weeks following transplantation. The apoptotic cells were detected in the myocardium by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL). BrdU-positive cells and the expression of Bcl-2 and Bax proteins were identified in the myocardium by immunohistochemical method.
RESULTS AND CONCLUSION: ①Compared with control group, cardiac functions were significantly improved in the transplantation group. ②BrdU-positive cells were found surrounding infarct site in the transplantation group. ③Compared with the control group, Bcl-2 protein levels were significantly increased, but Bax protein levels were significantly decreased in the transplantation group. ④Number of apoptotic cardiomyocytes was significantly less in the transplantation group than the control group at 4 weeks following transplantation. These verified that HUCBCs by intravenous administration migrate into the peri-infarcted area, and regulate the expression of Bcl-2 and Bax proteins, and inhibit cardiomyocyte apoptosis in the peri-infarcted area, and finally improve cardiac function following myocardial infarction.

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