中国神经再生研究(英文版) ›› 2015, Vol. 10 ›› Issue (8): 1265-1270.doi: 0.4103/1673-5374.162759

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

骨髓间充质干细胞移植促进缺血性脑卒中内源性促红细胞生成素释放

  

  • 收稿日期:2015-07-27 出版日期:2015-08-24 发布日期:2015-08-24
  • 基金资助:

    中国国家自然科学基金项目(81371258) ,浙江省中医药研究项目(2015ZA061),浙江省教育厅项目(Y201431639)

Bone marrow mesenchymal stem cells transplantation promotes the release of endogenous erythropoietin after ischemic stroke

Wen Lv1, Wen-yu Li1,, Xiao-yan Xu1, Hong Jiang1, Oh Yong Bang2   

  1. 1 Department of Neurology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China
    2 Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
  • Received:2015-07-27 Online:2015-08-24 Published:2015-08-24
  • Contact: Wen-yu Li, M.D., Ph.D., lee_wenyu@zju.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81371258; a grant from the TCM General Research Project of Zhejiang Province of China, No. 2015ZA061; a grant from the Education of Zhejiang Province of China, Y201431639.
     

摘要:

为观察骨髓间充质干细胞移植是否通过刺激内源性促红细胞生成素而发挥修复保护缺血性脑损伤的作用。实验用大脑中动脉阻塞方法建立缺血性脑卒中大鼠模型,24h后尾静脉注射1×106人骨髓间充质干细胞。14d后发现人骨髓间充质干细胞可以促进大鼠缺血脑组织中内源性促红细胞生成素的释放。而缺血性脑卒中大鼠注射人骨髓间充质干细胞的同时,连续13d侧脑室注射3 μg/d可溶性促红细胞生成素受体,可阻断内源性促红细胞生成素的释放,并侧脑室下区新生神经元数量比同时注射人骨髓间充质干细胞和失活的热变性可溶性促红细胞生成素受体大鼠减少;去除粘合剂测试评分和改良神经功能缺损评分低于单独注射热变性可溶性促红细胞生成素受体大鼠,而与注射人骨髓间充质干细胞和热变性可溶性促红细胞生成素受体大鼠接近。因此认为骨髓间充质干细胞是通过促进内源性促红细胞生成素释放促进缺血性脑卒中后的神经发生而改善神经功能。

关键词:

Abstract:

This study investigated whether bone marrow mesenchymal stem cell (BMSC) transplantation protected ischemic cerebral injury by stimulating endogenous erythropoietin. The model of ischemic stroke was established in rats through transient middle cerebral artery occlusion. Twenty-four hours later, 1 × 106 human BMSCs (hBMSCs) were injected into the tail vein. Fourteen days later, we found that hBMSCs promoted the release of endogenous erythropoietin in the ischemic region of rats. Simultaneously, 3 μg/d soluble erythropoietin receptor (sEPOR) was injected into the lateral ventricle, and on the next 13 consecutive days. sEPOR blocked the release of endogenous erythropoietin. The neurogenesis in the subventricular zone was less in the hBMSCs + sEPOR group than in the hBMSCs + heat-denatured sEPOR group. The adhesive-removal test result and the modified Neurological Severity Scores (mNSS) were lower in the hBMSCs + sEPOR group than in the heat-denatured sEPOR group. The adhesive-removal test result and mNSS were similar between the hBMSCs + heat-denatured sEPOR group and the hBMSCs + sEPOR group. These findings confirm that BMSCs contribute to neurogenesis and improve neurological function by promoting the release of endogenous erythropoietin following ischemic stroke.

 

Key words: nerve regeneration, stem cells, erythropoietin, ischemic stroke, erythropoietin receptor, cell proliferation, cytokine, BrdU, functional recovery, NSFC grant, neural regeneration