中国组织工程研究

中国组织工程研究 ›› 2013, Vol. 17 ›› Issue (19): 3481-3487.doi: 10.3969/j.issn.2095-4344.2013.19.010

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

人脐血单个核细胞静脉移植联合培哚普利对急性心肌梗死炎症反应的影响

邓柳霞1，2，余国龙1，艾 旗1，袁春菊1   

  1. 1 中南大学湘雅医院心内科，湖南省长沙市 410008 2 岳阳市第一人民医院心内科，湖南省岳阳市 414100
  • 收稿日期:2012-09-12 修回日期:2012-10-23 出版日期:2013-05-07 发布日期:2013-05-07
  • 通讯作者: 余国龙，教授，博士后，博士研究生导师，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:邓柳霞★，女，1985年生，湖南省岳阳市人，中南大学在读硕士，医师，主要从事冠心病防治基础与临床。 dengliuxia2008@yahoo.com.cn

Effects of intravenous transplantation of human umbilical cord blood mononuclear cells combined with perindopril on inflammatory response of acute myocardial infarction

Deng Liu-xia1, 2, Yu Guo-long1, Ai Qi1, Yuan Chun-ju1   

  1. 1 Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
    2 Department of Cardiology, First People’s Hospital of Yueyang, Yueyang  414100, Hunan Province, China
  • Received:2012-09-12 Revised:2012-10-23 Online:2013-05-07 Published:2013-05-07
  • Contact: Yu Guo-long, M.D., Professor, Doctoral supervisor, Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China yuguolong123@yahoo.com.cn
  • About author:Deng Liu-xia★, Studying for master’s degree, Physician, Department of Cardiology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China; Department of Cardiology, First People’s Hospital of Yueyang, Yueyang 414100, Hunan Province, China dengliuxia2008@yahoo.com.cn

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381

被引次数

3

摘要：

背景：近期报道骨髓间充质干细胞心肌内直接移植联合培哚普利治疗急性心肌梗死大鼠，可改善心肌组织内环境，并增强急性心肌梗死疗效。
目的：观察人脐血单个核细胞静脉移植联合血管紧张素转化酶抑制剂培哚普利对家兔急性心肌梗死心肌组织炎症反应与促炎因子白细胞介素6表达及心功能影响，并探讨联合治疗对急性心肌梗死可能的保护机制。
方法：人脐血单个核细胞取自健康足月分娩产妇脐血。60只健康家兔制备急性心肌梗死模型，建模成功后随机数字表法均分对照组、培哚普利组、单纯移植组和联合治疗组。每组随机选5只家兔分别于移植后1，2，4周超声心动图检测家兔心功能指标左室射血分数及左室短轴缩短率；苏木精-伊红染色光镜观察心肌病理变化和白细胞计数；免疫组化检测心肌组织白细胞介素6蛋白表达量；荧光显微镜观测绿色荧光蛋白阳性细胞。
结果与结论：①与对照组比较，培哚普利组、单纯移植组、联合治疗组治疗后1，2，4周心功能指标左室短轴缩短率及左室射血分数改善(P < 0.05)，单纯移植组高于培哚普利组(P < 0.05)，联合治疗组改善最显著(P < 0.05)。②与对照组比较，培哚普利组、单纯移植组、联合治疗组治疗后1，2，4周心肌组织白细胞计数及白细胞介素6的表达均显著减低(P < 0.05)，且单纯移植组低于培哚普利组(P < 0.05)，联合治疗组最低(P < 0.05)。③联合治疗组、单纯移植组治疗后1，2，4周均可见绿色荧光蛋白阳性细胞散在分布于梗死周边区域，且联合治疗组细胞计数多于单纯移植组(P < 0.05)。说明培哚普利联合人脐血单个核细胞静脉移植治疗急性心肌梗死实验动物，能提高移植细胞在心肌组织内存活率，并进一步改善心功能。其机制可能与联合治疗抑制心肌局部炎症反应及促炎因子白细胞介素6水平表达作用增强有关。

关键词: 干细胞, 干细胞移植, 心肌梗死, 脐血单个核细胞, 炎症反应, 培哚普利, 静脉移植, 白细胞介素6, 血管紧张素转化酶抑制剂, 心肌组织, 心肌细胞, 心室重塑, 干细胞图片文章

Abstract:

BACKGROUND: A recent study has indicated that angiotensin-converting enzyme inhibitor, perindopril, combined with transplantation of bone marrow-derived mesenchymal stem cells can reduce inflammatory response in the injured myocardium associated with enhanced improvement of cardiac function in an animal model of acute myocardial infarction. 
OBJECTIVE: To observe the effects of intravenous transplantation of human umbilical cord blood mononuclear cells combined with perindopril on the inflammatory responses and pro-inflammatory cytokine interleukin-6 expression as well as the cardiac function in rabbits with acute myocardial infarction, and to investigate the possible protective mechanism of the combination treatment for acute myocardial infarction.
METHODS: The human umbilical cord blood mononuclear cells were obtained from healthy full-term delivery maternal cord blood. Sixty healthy rabbits were selected to establish the models of acute myocardial infarction, and the models were divided into four groups randomly: control group, perindopril group, simple transplantation group and combination group. Five rabbits were selected from each group to detect the cardiac function index of left ventricular ejection fraction and left ventricular fractional shortening with echocardiography at 1, 2 and 4 weeks after treatment. Hematoxylin-eosin staining was performed to observe the myocardial pathological changes and white blood cell count under light microscope. The protein expression of interleukin-6 in myocardial tissue was detected with immunohistochemistry. The number of green fluorescent protein-positive cells was observed under fluorescence microscope.
RESULTS AND CONCLUSION: Compared with the control group, left ventricular ejection fraction and left ventricular fractional shortening were significantly improved in the perindopril group, simple transplantation group and combination group at 1, 2 and 4 weeks respectively after the treatment (P < 0.05). The improvement of cardiac function index in simple transplantation group was higher than that in the perindopril group and most significantly in the combination group among the three treatment groups (P < 0.05). Compared with the control group, the number of white blood cells and the expression of interleukin-6 were decreased significantly in the perindopril group, simple transplantation group and combination group (P < 0.05). The number of white blood cells and the expression of interleukin-6 were lower in the simple transplantation group than in the perindopril group (P < 0.05), and lowest in the combination group among the three treatment groups (P < 0.05). Green fluorescent protein-positive cells were found to distribute in the peri-myocardial infarction area in the simple transplantation group and combination group at 1, 2 and 4 weeks after treatment, and the number of the green fluorescent protein-positive cells in the combination group was more than that in the simple transplantation group. The findings indicate that the combination of intravenous transplantation of human umbilical cord blood mononuclear cells and perindopril in the treatment of rabbits with acute myocardial infarction can increase the survival rate of transplanted cells, and further enhance the improvement of the heart function. The possible mechanism may be relate to the combination treatment, which can inhibit the local myocardial inflammation response and the expression of pro-inflammatory cytokine, interleukin-6, effectively.

Key words: stem cells, stem cell transplantation, myocardial infarction, human umbilical cord blood mononuclear cells, inflammation response, perindopril, intravenous transplantation, interleukin-6, angiotensin-converting enzyme inhibitors, myocardial tissue, myocardial cells, ventricular remodeling, stem cell photographs-containing paper

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