中国组织工程研究

中国组织工程研究 ›› 2018, Vol. 22 ›› Issue (9): 1389-1394.doi: 10.3969/j.issn.2095-4344.0469

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

骨髓间充质干细胞移植对心肌梗死大鼠心肌钾离子通道蛋白和细胞因子的影响

胡继宏，赵静苗，王秋萍，贾 佳，路 娟，金 华，侯 茜   

  1. 甘肃中医药大学，甘肃省兰州市 730000
  • 修回日期:2017-10-18 出版日期:2018-03-28 发布日期:2018-04-03
  • 通讯作者: 胡继宏，博士，副教授，硕士生导师，甘肃中医药大学，甘肃省兰州市 730000
  • 作者简介:胡继宏，女，1976年生，湖北省武穴市人，汉族，2007年北京协和医学院毕业，博士，副教授，硕士生导师，主要从事心血管病防治研究。
  • 基金资助:

    国家自然科学基金(81260597)；甘肃省高校基本科研业务费项目(2012-3)

Effects of bone marrow mesenchymal stem cell transplantation on voltage-gated   K+ channel proteins and cytokines in the infarcted myocardium of rats

Hu Ji-hong, Zhao Jing-miao, Wang Qiu-ping, Jia Jia, Lu Juan, Jin Hua, Hou Qian   

  1. Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, Chin
  • Revised:2017-10-18 Online:2018-03-28 Published:2018-04-03
  • Contact: Hu Ji-hong, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
  • About author:Hu Ji-hong, M.D., Associate professor, Master’s supervisor, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
  • Supported by:

    the National Natural Science Foundation of China, No. 81260597; the Fundamental Research Foundation for Universities in Gansu Province, No. 2012-3

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摘要：

文章快速阅读：

文题释义：
延迟整流钾电流(Ik)：主要参与心肌细胞动作电位的复极过程，与心肌细胞动作电位时程和有效不应期的长短关系密切。其主要包含两种成分：快激活成分(Ikr)和慢激活成分(Iks)。它们的分子特点是心肌电生理特性的基础，组织分布特点是心肌细胞动作电位时程和有效不应期离散的基础。
电压门控离子通道：主要有钠、钾、钙等离子通道，通常由同一亚基的四个跨膜区段围成孔道，孔道中有一些带电基团(电位敏感器)控制闸门，当跨膜电位发生变化时，电敏感器在电场力的作用下产生位移，响应膜电位的变化，造成闸门的开启或关闭。孔道口的孔径和电荷分布形成离子选择器，但并非对其他离子绝对不通透。

 

摘要
背景：研究表明，骨髓间充质干细胞移植可以有效改善心肌梗死后的心功能，移植后的骨髓间充质干细胞可能对心肌电生理有一定影响，但目前相关的研究甚少。
目的：观察骨髓间充质干细胞移植对心肌梗死大鼠心肌钾离子电压门控通道蛋白和心肌梗死相关细胞因子的影响，为进一步探索骨髓间充质干细胞治疗心肌梗死引起心律失常的相关机制提供研究基础。  
方法：将40只SPF级Wistar雄性大鼠随机分为假手术组、模型组、细胞培养液组和骨髓间充质干细胞组。通过冠状动脉左前降支结扎建立心肌梗死模型，并于建模成功15-20 min后在梗死区周围采用四点法注射100 µL骨髓间充质干细胞悬液(含1×106个骨髓间充质干细胞)和100 µL细胞培养液。细胞移植4周后获取心脏标本，采用苏木精-伊红染色观察梗死心肌组织病理形态并计算梗死面积，采用Westernn blot检测钾离子电压门控通道蛋白Kv1.2和Kv1.5和心肌细胞特异性蛋白cTnT的表达，利用免疫组化方法检测梗死区心肌细胞凋亡因子Caspase-3、自噬因子Bcl-2 和一氧化氮及超氧化物歧化酶的表达。
结果与结论：①与模型组相比，骨髓间充质干细胞组心肌梗死面积减小(P < 0.05)，cTnT、Kv1.5和超氧化物歧化酶表达水平均提高(P < 0.05)，Caspase-3、Bcl-2和Kv1.2表达水平均降低(P < 0.05)；②与细胞培养液组比较，骨髓间充质干细胞组心肌梗死面积减小(P < 0.05)，cTnT、Kv1.5和超氧化物歧化酶表达水平均提高(P < 0.05)，Caspase-3、Bcl-2和Kv1.2表达水平均降低(P < 0.05)；③结果提示，骨髓间充质干细胞移植提高了心肌抗氧化能力，减少了细胞凋亡和自噬，促进钾离子通道蛋白Kv1.5的表达。

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
ORCID: 0000-0003-2729-9711(胡继宏)

关键词: 干细胞, 心肌梗死, 骨髓间充质干细胞, Kv1.5, Kv1.2, 细胞自噬, 细胞凋亡, 国家自然科学基金

Abstract:

BACKGROUND: Studies have shown that bone marrow mesenchymal stem cell (BMSC) transplantation can effectively improve cardiac function after myocardial infarction. However, few reports have been issued on myocardial electrophysiology after BMSCs transplantation. 
OBJECTIVE: To observe the effects of BMSCs transplantation on voltage-gated K+ channel protein and myocardial infarction-related cytokines, thereby providing basic evidence for further exploration on the mechanism underlying arrhythmia in myocardial infarction due to BMSCs transplantation. 
METHODS: Forty male Wistar rats, SPF grade, were randomly divided into four groups: sham group, model group, cell culture medium group and BMSCs group. The myocardial infarction model was created in rats by permanent ligation of the left descending coronary artery. At 15-20 minutes after surgery, BMSCs (100 µL, 1×106) or cell culture medium (100 µL) was injected at four sites in the peri-infarct zone. Four weeks after cell therapy, cardiac samples were taken, the pathological morphology of the infarcted myocardium was observed by hematoxylin-eosin staining, and the infarct size was calculated; the expression levels of voltage-gated K+ channel proteins Kv1.2 and Kv1.5 and cardiac troponin T (cTnT) were measured by western blot assay; and the expression levels of apoptotic factor (Caspase-3), autophagy factor (Bcl-2), nitric oxide and superoxide dismutase were tested by immunohistochemistry. 
RESULTS AND CONCLUSION: Compared with the model group and cell culture medium group, the infarct size decreased in the BMSCs group (P < 0.05); the expression levels of cTnT, Kv1.5 and superoxide dismutase increased (P < 0.05), and the expression levels of Caspase-3, Bcl-2 and Kv1.2 decreased (P < 0.05) in the BMSCs group. In summary, BMSCs transplantation can promote the expression of voltage-gated K+ channel proteins, and improve anti-oxidation capacity of the myocardium and decrease apoptosis and autophagy. 

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

Key words: Bone Marrow, Mesenchymal Stem Cell Transplantation, Myocardial Infarction, Potassium Channels, Voltage-Gated, Apoptosis, Tissue Engineering

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