中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (17): 2625-2630.doi: 10.3969/j.issn.2095-4344.2017.17.001

• 骨髓干细胞 bone marrow stem cells •    下一篇

肝X受体激活修复丙泊酚对骨髓间充质干细胞的抑制作用

张永强，刘  俊，陈胜阳，刘国泽，田建民，岳修勤   

  1. 新乡医学院第一附属医院麻醉科，河南省卫辉市  453100
  • 修回日期:2017-01-26 出版日期:2017-06-18 发布日期:2017-06-29
  • 通讯作者: 岳修勤，主任医师，新乡医学院第一附属医院麻醉科，河南省卫辉市 453100
  • 作者简介:张永强，男，1975年生，河南省新乡市人，汉族，硕士，副主任医师，主要从事围术期器官保护研究。
  • 基金资助:

    河南省教育厅自然科学研究计划项目(2013B202306)

Liver X receptor reverses the inhibitory effects of propofol on bone marrow mesenchymal stem cells

Zhang Yong-qiang, Liu Jun, Chen Sheng-yang, Liu Guo-ze, Tian Jian-min, Yue Xiu-qin   

  1. Department of Anesthesiology, First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
  • Revised:2017-01-26 Online:2017-06-18 Published:2017-06-29
  • Contact: Yue Xiu-qin, Chief physician, Department of Anesthesiology, First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
  • About author:Zhang Yong-qiang, Master, Associate chief physician, Department of Anesthesiology, First Affiliated Hospital of Xinxiang Medical University, Weihui 453100, Henan Province, China
  • Supported by:

     the Natural Science Research Plan of Henan Provincial Education Department, No. 2013B202306

PDF

234

摘要：

文章快速阅读：

文题释义：
肝X受体：包括肝X受体α和肝X受体β两型，属于配体激活的转录因子家族，近年发现其在中枢神经系统发育中有重要作用。已证实肝X受体预处理保护小脑中Bergmann胶质细胞(类似于海马中放射状胶质细胞)免于酒精毒性作用，进而促进小脑的发育，且肝X受体β缺失影响胚胎发育中海马齿回神经干细胞的发育。
丙泊酚对间充质干细胞的机制作用：丙泊酚是目前临床上普遍用于麻醉诱导、麻醉维持、ICU危重患者镇静的一种新型快速短效静脉麻醉药，其具有麻醉诱导起效快、苏醒迅速且功能恢复完善，术后恶心呕吐发生率低等优点。4岁以下儿童使用丙泊酚可能会影响骨骼生长，致机体发育障碍。间充质干细胞是体内生长发育相关键的一类重要细胞。有研究已证实，丙泊酚可减少成年大鼠间充质干细胞的数量，同时与间充质干细胞相关的分化也受到显著抑制。

 

摘要
背景：研究已证实，丙泊酚可减少成年大鼠间充质干细胞的数量，同时与间充质干细胞相关的分化也显著受到抑制。
目的：探究肝X受体是否可激活修复丙泊酚对骨髓间充质干细胞的抑制作用。
方法：将15只新生C57/BL6小鼠随机分为3组，空白对照组腹腔注射生理盐水；对照组腹腔注射丙泊酚60 mg/kg；实验组首先腹腔注射肝X受体激动剂10 μL/g，隔天注射丙泊酚60 mg/kg。注射1-3 h后处死3组小鼠，分离培养骨髓间充质干细胞，CCK-8及克隆形成实验检测细胞增殖及自我更新情况；检测3组细胞的成脂、成骨及成软骨能力；实时定量PCR检测3组细胞诱导分化前、诱导分化后的Notch信号表达，以及加入Notch通路抑制剂后，成脂、成骨及成软骨诱导分化后的相关基因表达。
结果与结论：①与空白对照组比较，对照组骨髓间充质干细胞增殖与克隆形成能力显著降低(P < 0.05)；与对照组比较，实验组骨髓间充质干细胞增殖与克隆形成能力显著升高(P < 0.05)；②与空白对照组比较，对照组骨髓间充质干细胞成脂、成骨及成软骨能力显著降低(P < 0.05)；与对照组比较，实验组骨髓间充质干细胞成脂、成骨及成软骨能力显著升高(P < 0.05)；③诱导分化前，3组间Notch信号表达无差异。诱导分化后，与空白对照组比较，对照组骨髓间充质干细胞成脂、成骨及成软骨分化相关基因表达显著下调(P < 0.05)；与对照组比较，实验组骨髓间充质干细胞成脂、成骨及成软骨分化相关基因表达显著上调(P < 0.05)。加入Notch通路抑制剂后，3组细胞成脂、成骨及成软骨诱导分化均受抑制；④结果表明，肝X受体激活可修复丙泊酚对骨髓间充质干细胞的抑制作用。

 

 

ORCID: 0000-0002-4130-1681(岳修勤)

关键词: 干细胞, 骨髓干细胞, 肝X受体, 骨髓间充质干细胞, 丙泊酚, 自我更新, 分化

Abstract:

BACKGROUND: Studies have shown that propofol enables a reduction in the number of adult rat mesenchymal stem cells, while the cell differentiation is also significantly inhibited.
OBJECTIVE: To explore whether liver X receptors (LXRs) can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells.
METHODS: Fifteen healthy C57/BL6 mice were randomized into three groups, 5 of which served as blank control group (intraperitoneally treated with normal saline), 5 as propofol treatment group (intraperitoneally treated with 60 mg/kg propofol), and 5 as propofol + LXRs agonist treatment group (intraperitoneally injected with 10 μL/g LXRs at the 1st day, and then injected with 60 mg/kg propofol at the 2nd day). The mice in the three groups were killed at 1-3 hours after treatment to isolate and culture bone marrow mesenchymal stem cells. Cell counting kit-8 and clone formation assay were used to evaluate the abilities of cell proliferation and self-renewal; induced differentiation experiments in vitro were used to evaluate the differentiation ability of cells into adipocytes, osteoblasts and chondrocytes; real-time quantitative PCR was used to detect the expression of differentiation related molecules and Notch signal.
RESULTS AND CONCLUSION: In the propofol-treated mice, cell viability and clone forming ability as well as adipogenic, osteogenic and chondrogenic differentiation of cells decreased significantly compared with the blank control group (P < 0.05), while LXR agonists could reverse these effects significantly (P < 0.05). Notch signal expressions showed no difference among three groups prior to induced differentiation. The expression levels differentiation related molecules downregulated significantly after propofol treatment (P < 0.05), but upregulated significantly after treatment with LXR agonists (P < 0.05). Notch signaling inhibitor treatment could significantly inhibit the multi-directional differentiation of bone marrow mesenchymal stem cells in the three groups. All these findings indicate that activated LXRs can reverse the inhibitory effects of propofol on bone marrow mesenchymal stem cells.

 

 

Key words: Stem Cells, Propofol, Mesenchymal Stem Cells, Tissue Engineering

中图分类号: