实用医学杂志 ›› 2023, Vol. 39 ›› Issue (6): 660-666.doi: 10.3969/j.issn.1006⁃5725.2023.06.002

• 基础研究 • 上一篇    下一篇

过表达NKx2.5 CXCR 基因间充质干细胞增强SDF⁃1/ 4轴促归巢改善心梗心功能 

陈霞1 武馨馨2 刘星佑2 陈鑫昊1 黄尹霞1 肖志原3 贺继刚2    

  1. 昆明理工大学附属医院、云南省第一人民医院1 心脏大血管外科，3 内科重症医学科（昆明 650000）； 2 云南中医药大学（昆明 650000）

  • 出版日期:2023-03-25 发布日期:2023-03-25
  • 通讯作者: 贺继刚 E⁃mail：jiganghe999@163.com；肖志原 E⁃mail：jiganghe@sina.com
  • 基金资助:

    国家自然科学基金项目（编号：82060299）；云南省卫生健康委员会医学学科带头人项目（编号：D⁃2019020）；云南省政府万人计划-青年拔尖人才项目（编号：KH⁃SWR⁃QNBJ⁃2019⁃002）；云南省第一人民医院临床医学中心开放项目（编号：2021LCZXXF⁃XZ04，2022LCZXKF⁃HX05）；昆医联合专项-杰出青年培育项目（编号：202101AY070001⁃034）；云南省“兴滇英才支持计划”名医专项（编号：XDYC⁃MY⁃2022⁃0037）

Overexpressed NKx2.5 genes in mesenchymal stem cells improve myocardial function in patients with myo⁃ cardial infarction via enhancing SDF⁃1/CXCR4⁃axis homing

CHEN Xia*，WU Xinxin，LIU Xingyou，CHEN Xinhao，HUANG Yinxia，XIAO Zhiyuan，HE Jigang.    

  1. Department of Cardiovascular Surgery，the Affiliated Hospital of Kunming Vunirersity of Science and Technology，the First People′ s Hospital of Yunnan Province，Kunming 650000，China

  • Online:2023-03-25 Published:2023-03-25
  • Contact: HE Jigang E⁃mail：jiganghe999@163.com；XIAO Zhiyuan E⁃mail：jiganghe@sina.com

摘要：

目的 探讨过表达 NKx2.5 基因骨髓间充质干细胞（BMSC）通过增强 SDF⁃1/CXCR4 轴促 BMSC 归巢改善心梗后心功能。方法 采用慢病毒使骨髓间充质干细胞内过表达 NKx2.5（BMSCNKx2.5 ），将空载体组及 BMSC 组作为对照组。采用 RT⁃PCR 检测各组细胞 SDF⁃1、CXCR4 及 NKx2.5 的表达及同时采用 western⁃blot 检测 NKx2.5 及 SDF⁃1、CXCR4 蛋白的表达。将 BMSCNKx2.5 、BMSC、及 BMSC 空载体经尾静脉注射入小鼠心梗模型，同时设立 BMSCNKx2.5 +AMD3100 组，将心梗未处理组、假手术组、正常小鼠组作为对照组。 采用心脏彩超检测心梗小鼠心功能的变化及采用 western blot 检测 NKx2.5 及 SDF⁃1、CXCR4 蛋白的表达。 结果 体外BMSCNKx2.5 组SDF⁃1及CXCR4及转录因子NKx2.5的表达最高（P < 0.05）。体内实验证实BMSCNKx2.5 组心梗心功能改善最为明显（P < 0.05），但当加入SDF⁃1⁃CXCR4轴抑制剂AMD3100后，心功能改善不明显。 BMSCNKx2.5 组转录因子NKx2.5及SDF⁃1及CXCR4因子的表达最高（P < 0.05），但加入AMD3100组后SDF⁃1及CXCR4的表达明显下降。结论 BMSCNKx2.5 可以通过增强SDF⁃1/CXCR4轴促BMSC归巢改善心梗心功能。

关键词:

NKx2.5, SDF?1/CXCR4轴, 骨髓间充质干细胞, 归巢, 心肌梗死

Abstract:

Objective To investigate the effect of the overexpressed NKx2.5 genes in bone marrow mesen⁃ chymal stem cells（BMSCs）on cardiac function after myocardial infarction by enhancing the SDF⁃1/CXCR4 axis to promote BMSC homing. Methods Lentivirus was used to overexpress NKx2.5 in BMSCs（BMSCNKx2.5 ）. The empty body group，BMSC group，and mouse cardiomyocyte group were used as the control groups. The expressions of SDF⁃1，CXCR4 and NKx2.5 in each group were detected by RT⁃PCR，and the expression of transcription factors NKx2.5，SDF⁃1 and CXCR4 proteins was detected by western⁃blot. BMSCNKx2.5 ，BMSC，and BMSCempty body were injected into the mouse myocardial infarction model through the tail vein. The BMSCNKx2.5 +AMD3100 group was set up. The untreated myocardial infarction group，sham operation group，and normal mouse group were used as the control groups. Changes in the cardiac function of mice with myocardial infarction were detected via Color Dop⁃ pler ultrasound. The expression of NKx2.5，SDF ⁃ 1 and CXCR4 proteins was detected by western ⁃ blot. Results NKx2.5，SDF ⁃1 and CXCR4 in the BMSCNKx2.5 group had the highest expression（P < 0.05）. In vivo experiments confirmed that the BMSCNKx2.5 group exhibited the most significant improvement in cardiac function after myocardial infarction（P < 0.05）. The expression of transcription factors NKx2.5，SDF⁃1 and CXCR4 in BMSCNKx2.5 group was the highest（P < 0.05）. However，when the SDF⁃1⁃CXCR4 axis inhibitor AMD3100 was added，the improvement in cardiac function was insignificant. Conclusion BMSCNKx2.5 can improve myocardial function after myocardial infarction by enhancing the SDF⁃1/CXCR4 axis to promote BMSC homing.


Key words:

text-indent:0.0000pt, text-align:justify, "> NKx2.5, SDF?1/CXCR4 axis, bone marrow mesenchymal stem cells, homing, myo? cardial infarction ,

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