中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (3): 434-439.doi: 10.4103/1673-5374.228725

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

孕酮调节创伤性脑损伤小鼠海马雷帕霉素机制性靶标的表达

  

  • 收稿日期:2018-01-23 出版日期:2018-03-15 发布日期:2018-03-15

Progesterone modulates mTOR in the hippocampus of mice after traumatic brain injury

Richard Justin Garling1, 2, Lora Talley Watts2, Shane Sprague3, Murat Digicaylioglu3   

  1. 1 Department of Neurosurgery, Wayne State University, Detroit, MI, USA
    2 School of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
    3 Department of Neurosurgery, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA
  • Received:2018-01-23 Online:2018-03-15 Published:2018-03-15
  • Contact: Richard Justin Garling, M.D.,Jgarling@med.wayne.edu.

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摘要：

 雷帕霉素机制性靶标（mTOR）是一种细胞内丝氨酸/苏氨酸蛋白激酶，为神经元细胞微环境中的能量和营养感应器，当营养物质和能源变得有限时，调节mTOR的表达对于保证神经元的存活至关重要。已有研究证实，疏水性类固醇激素黄体酮（P4）在非神经组织可调节mTOR的表达。为研究黄体酮对创伤性损伤脑组织mTOR表达的影响，实验应用气动冲击式颅脑损伤装置建立闭合性创伤性脑损伤C57BL/6小鼠模型，并于伤后1h腹腔注射，6，24，48h皮下注射黄体酮（8mg/kg），并设假手术组为对照。损伤后72h应用免疫印迹方法检测发现，相较于假手术组，黄体酮显著降低了创伤性脑损伤小鼠海马总mTOR蛋白表达水平，免疫荧光染色进一步验证了免疫印迹检测结果，显示胞质mTOR水平也明显降低。从而说明P4是创伤性脑损伤小鼠海马组织中mTOR水平的调节剂。

orcid:0000-0002-2685-531X(Richard Justin Garling)

关键词: 闭合性颅骨损伤, 神经创伤, 类固醇激素, 气压伤模型, 雷帕霉素, 脑损伤, 神经保护, 神经再生

Abstract:

The mechanistic target of rapamycin (mTOR) is an intracellular protein kinase that functions as an energy and nutrient sensor in the cellular microenvironment of neurons. Modulation of mTOR is vital when nutrient and energy sources become limited. Hypoxia, traumatic brain injury, cellular energy states, and growth factors all regulate the phosphorylation and total levels of mTOR in cells. Alterations in the microenvironment induce transduction of signals to downstream proteins by mTOR allowing for cells to make the necessary adjustments to counteract stressors and survive. Progesterone, a hydrophobic steroid hormone, has been shown in studies of non-neural tissue to be a suppressor of mTOR and modulator of mTOR phosphorylation. Our study tested the effects of progesterone on mTOR expression following traumatic brain injury. C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitoneal), 6 (subcutaneous), 24 (subcutaneous), and 48 (subcutaneous) hours post closed skull traumatic brain injury.The hippocampus was then harvested 72 hours post injury and prepared for western blot analysis. We found that progesterone significantly decreased total mTOR levels in all groups compared to sham treated with vehicle. This was further confirmed by immunostaining showing decreased cytoplasmic mTOR levels compared to sham. Our study shows progesterone

Key words: nerve regeneration, traumatic brain injury, closed skull head injury, neurotrauma, progesterone, pneumatic injury model, neuroprotection, neural regeneration