上海交通大学学报（医学版）

上海交通大学学报（医学版） ›› 2017, Vol. 37 ›› Issue (12): 1608-.doi: 10.3969/j.issn.1674-8115.2017.12.005

• 论著（基础研究） • 上一篇    下一篇

骨髓间充质干细胞对缺氧缺血性脑损伤海马组织中自噬的调节作用

杨 苗 1, 2, 3，何慕兰 1, 2, 3，谷 燕 1, 2, 3，杨 亭 1, 2，李廷玉 1, 2，陈 洁 1, 2, 3   

  1. 1. 重庆医科大学附属儿童医院儿童营养研究中心，2. 儿童发育疾病研究教育部重点实验室，3. 重庆市干细胞治疗工程技术研究中心，重庆
    400014
  • 出版日期:2017-12-28 发布日期:2018-01-10
  • 通讯作者: 陈 洁，电子信箱：jchen010@hospital.cqmu.edu.cn
  • 基金资助:
     国家自然科学基金面上项目（81470799）

Modulation of mesenchymal stem cells on autophagy in hippocampus of rats with hypoxic-ischemic #br# brain damage

YANG Miao1, 2, 3, HE Mu-lan1, 2, 3, GU Yan1, 2, 3, YANG Ting1, 2, LI Ting-yu1, 2, CHEN Jie1, 2, 3   

  1. 1. Children’s Nutrition Research Center, Children’s Hospital of Chongqing Medical University; 2. Ministry of Education Key Laboratory in Child Development and Disorders;
    3. Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing 400014, China
  • Online:2017-12-28 Published:2018-01-10
  • Supported by:
    National Natural Science Foundation of China, 81470799

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摘要： [ 摘要 ] 目的 ·   探讨骨髓间充质干细胞（MSCs）对缺氧缺血性脑损伤（HIBD）新生大鼠海马自噬的作用。方法 ·   Western blotting 检测MSCs 移植 HIBD 大鼠海马及共培养后氧糖剥夺（OGD）损伤海马神经元中 Beclin1、LC3 Ⅱ、p62 蛋白表达变化，Morris 水迷宫检测大鼠学习记忆功能，透射电子显微镜观察共培养后的 OGD 损伤神经元中自噬小体数量。结果 ·   HIBD 损伤 12 ～ 24 h 后的大鼠海马组织自噬相关蛋白 Beclin1 、LC3 Ⅱ蛋白表达水平显著上调，MSCs 移植后明显抑制损伤海马中上调的自噬水平，改善 HIBD 大鼠的学习记忆功能。同样，体外 OGD 损伤 12 h 也可诱导原代海马神经元 Beclin1、LC3 Ⅱ蛋白表达水平，MSCs 分离共培养后显著下调损伤海马神经元中的相关自噬水平，减少自噬小体的数量。结论 ·  MSCs 可能通过调控损伤微环境，抑制海马神经元的自噬，促进 HIBD大鼠的学习记忆功能修复。

关键词: &ensp, 骨髓间充质干细胞；缺氧缺血性脑损伤；自噬；学习记忆功能

Abstract:

[Abstract] Objective · To investigate the effect of mesenchymal stem cells (MSCs) on autophagy in hippocampus of neonatal rats with hypoxic-ischemic
brain damage (HIBD). Methods · Western blotting was used to detect the expression levels of autophagy associated proteins Beclin1, LC3 Ⅱ , and p62 in
the hippocampus of HIBD rats following MSCs transplantation and oxygen glucose deprivation (OGD)-injured primary neurons following MSCs seperated
coculture. The learning-memory function in the HIBD rats after MSCs transplantation was tested by Morris water maze test. Transmission electron
microscopy was also used to observe the number of autophagic neurons in OGD damaged neurons after coculture with MSCs. Results · The levels
of Beclin1 and LC3 Ⅱ protein expressions were significantly increased at 12-24 h in the rat hippocampus following HIBD injury. MSCs transplantation
statistically downregulated the autophagy level in the hippocampus, and obviously improved the learning-memory function of HIBD rats. Meanwhile, the
levels of Beclin1 and LC3 Ⅱ protein expressions in the primary neurons in vitro were also induced by OGD for 12 h. MSCs seperated coculture significantly
downregulated the autophagy level of hippocampal neurons by OGD injury, decreased the number of autophagosome in the OGD-injured neurons.
Conclusion · MSCs may inhibit the autophagy of hippocampal neurons by partly regulating the damaged microenvironment to improve the learning and
memory function of HIBD rats.

Key words: mesenchymal stem cell, hypoxic-ischemic brain damage, autophagy, learning and memory function