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《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:

2012年第6期

页码:

691-695

栏目:

基础研究

出版日期:

2012-12-25

文章信息/Info

Title:

In vivo visualization of apelin in survival and function of adipose-derived mesenchymal stem cells in hind limb of ischemic mice

作者:

梁 栋¹; 段红莉²; 秦 星¹; 程 康¹; 马 珂¹; 刘 通¹; 曹 丰¹

(1.第四军医大学西京医院心血管内科，陕西 西安 710032；2.西安市临潼区人民医院心内科，陕西 西安 710600)

Author(s):

LIANG Dong¹;  DUAN Hong-li²;  QIN Xing¹;  CHENG Kang¹;  MA Ke¹;  LIU Tong¹;  CAO Feng¹

(1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China; 2.Department of Cardiology, People’s Hospital, Lintong District, Xi’an 710600, Shaanxi, China)

关键词:

apelin; 分子影像; 间充质干细胞; 缺血

Keywords:

apelin;  molecular imaging;  mesenchymal stem cells;  ischemia

分类号:

Q463;Q253

DOI:

-

文献标识码:

A

摘要:

目的:探讨apelin对于脂肪间充质干细胞(AD-MSCs)修复小鼠后肢缺血损伤的作用及机制。方法： 从β-actin-luc转基因小鼠中分离出表达荧光素酶的AD-MSCs，将20只近交系无报告基因的小鼠随机分为两组，即实验组：后肢注射AD-MSCs+apelin(n=10)和对照组：后肢注射AD-MSCs(n=10)。所有小鼠均结扎股动脉建立后肢缺血模型，股四头肌内注射AD-MSCs(1×106)或AD-MSCs+apelin，激光多普勒成像观察下肢血液灌注，生物发光成像检测细胞的活性。用体外培养的β-actin-luc转基因小鼠AD-MSCs，建立缺氧（6 h）模型。实验分为4组，即对照组、缺氧组、缺氧＋apelin干预组及缺氧＋apelin+LY294002组。用免疫印迹法检测细胞内激酶磷酸化Akt 的表达。结果： 在移植后1周内生物发光成像显示，AD-MSCs移植后存在急性死亡，加用apelin组中细胞的存活时间明显延长。离体实验显示，在缺氧环境中apelin干预AD-MSCs后，细胞pAkt的表达明显高于对照组(P<0.05)，加入Akt阻断剂LY294002后，细胞磷酸化的水平降低(P<0.05)。结论： apelin对AD-MSCs的后肢缺血治疗具有保护作用，可能在缺血性疾病的治疗中成为重要的干预靶点。

Abstract:

AIM:To evaluate the contribution of apelin, a novel peptide with significant cardioactive properties and the therapeutic efficacy of mesenchymal stem cells in hind limb ischemia mice. METHODS: Adipose-derived mesenchymal stem cells (AD-MSCs) expressing firefly luciferase (Fluc) were isolated from β-actin-luc mice and characterized by flow cytometry and bioluminescence imaging (BLI). Male FVB mice underwent femoral artery ligation and received AD-MSCs (1×106) or AD-MSCs with apelin intraquadriceps femoris muscle injection. Cell survival was imaged by BLI and expressions of Akt and pAkt after cellular therapy were analyzed by Western blot. RESULTS: In vivo BLI revealed acute donor cell death of AD-MSCs within 1 week after transplantation. In contrast, signals of injected cells were still present after 1 week in AD-MSCs in apelin group (P<0.05). In vitro apelin treatment of AD-MSCs exposed to hypoxia increased cell proliferation and considerable increases in phosphorylation of Akt were found in AD-MSCs pretreated with apelin. CONCLUSION: Apelin has beneficial effects on the therapeutic efficacy and survival maintenance of AD-MSCs in hind limb ischemia and may constitute an important target therapy in ischemic disease.

参考文献/References

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备注/Memo

备注/Memo:

收稿日期：2012-09-01.通讯作者：曹丰，主任医师，主要从事冠心病诊断治疗及分子影像学研究Email:wind8828@gmail.com 作者简介：梁栋，住院医师，博士生 Email:liangdongld@gmail.com 共同第一作者：段红莉，主治医师，硕士生 Email:1062283267@qq.com

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更新日期/Last Update: 2012-12-30