中国组织工程研究

中国组织工程研究 ›› 2015, Vol. 19 ›› Issue (23): 3698-3704.doi: 10.3969/j.issn.2095-4344.2015.23.016

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

吡格列酮联合骨髓间充质干细胞移植治疗改善大鼠心肌梗死后的心功能

伍权华，侯婧瑛，郭天柱，钟婷婷，龙会宝，邢  越，周长青，郑韶欣，王  彤   

  1. 中山大学孙逸仙纪念医院急诊科，广东省广州市  510120
  • 出版日期:2015-06-04 发布日期:2015-06-04
  • 通讯作者: 王彤，博士，博士生导师，教授，主任医师，研究员，中山大学孙逸仙纪念医院急诊科，广东省广州市 510120
  • 作者简介:伍权华，男，1973年生，广东省恩平市人，汉族，中山大学孙逸仙纪念医院在读硕士，主治医师，主要从事急诊医学专业方面的研究。
  • 基金资助:

    国家自然科学基金(81070125)“抗凋亡与促血管生成miRNA-378干预MSCs治疗心梗后心衰的机制研究”；国家自然科学基金(81270213)“ANGⅡ/AT1/SMAD/CX43通路在心肌干细胞提高心梗大鼠心电生理学稳定性和室颤阈值的作用机制研究”；广东省科技计划项目(2010B031600032)“抗凋亡与促血管生成miRNA-378干预MSCs治疗心梗后心衰的机制研究”；高校基本科研业务费中山大学青年教师重点培育项目(13ykzd16) “PPAR-γ/TGF-β1/Smad/CX43通路在PPAR-γ干预MSCs治疗心梗后心衰的疗效及机制研究”

Pioglitazone administration combined with bone marrow mesenchymal stem cells transplantation improved the heart function of rats with myocardial infarction 

Wu Quan-hua, Hou Jing-ying, Guo Tian-zhu, Zhong Ting-ting, Long Hui-bao, Xing Yue, Zhou Chang-qing, Zheng Shao-xin, Wang Tong   

  1. Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
  • Online:2015-06-04 Published:2015-06-04
  • Contact: Wang Tong, M.D., Doctoral supervisor, Professor, Chief physician, Researcher, Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
  • About author:Wu Quan-hua, Studying for master’s degree, Attending physician, Department of Emergency, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, Guangdong Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81070125, 81270213; the Science and Technology Plan of Guangdong Province, No. 2010B031600032; the Fundamental Research Funds for Young Teacher Culture in Sun Yat-sen University, No. 13ykzd16

PDF

329

被引次数

5

摘要：

背景：前期研究发现骨髓间充质干细胞移植能够改善心肌梗死大鼠的心功能，但整体效果并不太理想。
目的：拟采用PPAR-γ激动剂吡格列酮联合骨髓间充质干细胞移植治疗以进一步改善心肌梗死大鼠的心功能并探讨相关机制。
方法：开胸结扎20只SD大鼠左前降支冠状动脉并随机分为2组：骨髓间充质干细胞组和骨髓间充质干细胞+吡格列酮组。2周后在局部梗死心肌内注射PKH26标记的由PBS悬浮的骨髓间充质干细胞，联合治疗组在注射骨髓间充质干细胞后予以吡格列酮3 mg/(kg•d)连续灌胃2周。细胞移植后2周进行超声心动图检测，免疫荧光染色、Western blot、qRT-PCR检测左心室心肌组织不同区域PPAR-γ、TGF-β1/SMAD通路相关因子和Cx43的表达情况。
结果与结论：两组大鼠基础心功能参数无明显差异性。细胞移植2周后，骨髓间充质干细胞+吡格列酮组左室舒张末径、左室收缩末径明显减小，左室射血分数明显增高；左心室心肌组织不同区域PPAR-γ和Cx43的表达量显著增加；TGF-β1、SMAD2、SMAD3在梗死区和梗死边缘区表达明显下降。以上结果提示PPAR-γ激动剂吡格列酮干预能够增强骨髓间充质干细胞移植对心功能的改善作用，其机制可能与PPAR-γ抑制TGF-β1/SMAD通路进而提高Cx43的表达有关。

 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 干细胞, 移植, 过氧化物酶体增殖物激活受体γ, 骨髓间充质干细胞, 心肌梗死, 转化生长因子β1, 缝隙连接蛋白43, 国家自然科学基金

Abstract:

BACKGROUND: Our previous work has demonstrated that bone marrow mesenchymal stem cells (BMSCs) transplantation can improve the heart function of rats with myocardial infarction. However, the overall efficacy is not satisfactory.
OBJECTIVE: To adopt pioglitazone as a peroxisome proliferator-activated receptor gamma (PPAR-γ) agonist combined with BMSCs transplantation therapy, thereby further improving cardiac function of rats with myocardial infarction as well as investigating the relevant mechanisms.
METHODS: Twenty Sprague-Dawley rats with myocardial infarction were induced by the left anterior descending coronary artery ligation. The animals were randomized into two groups: BMSCs and BMSCs+pioglitazone. Two weeks later, all the animals received the injection of BMSCs labeled with PKH26 in PBS into the local infarct zone, and then pioglitazone
(3 mg/kg/d) was given by the oral gavage for 2 weeks in the BMSCs+pioglitazone group after the cell transplantation. After 2 weeks of cell transplantation, cardiac functions were evaluated by echocardiography. The expressions of PPAR-γ, Connexin 43 and molecules in TGF-β1/SMAD signaling pathway were examined in different areas of the left ventricle from each harvested heart using immunofluorescent staining, western blot assay and qRT-PCR.
RESULTS AND CONCLUSION: There were no differences in the baseline parameters of cardiac function between the two groups. At 2 weeks after cell transplantation, the left ventricular internal diameter at end-diastole, left ventricular internal diameter at end-systole and left ventricular ejection fraction were significantly improved in the BMSCs+ pioglitazone group; the expressions of PPAR-γ and Connexin 43 were distinctly increased in different zones of the left ventricle; the levels of TGF-β1, SMAD2 and SMAD3 were obviously attenuated in the infarct zone and border zone. The above-mentioned findings suggest that pioglitazone, a PPAR-γ agonist, can enhance BMSCs potential in improving the heart function after myocardial infarction, and PPAR-γ may elevate the expression of Connexin 43 via the blockade of the TGF-β1/SMAD signaling pathway in the procedure.

 中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

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