中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (21): 1891-1896.doi: 10.4103/1673-5374.145355

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

孕酮干预脑创伤大鼠海马Akt磷酸化水平明显提高:是其神经保护途径?

  

  • 收稿日期:2014-09-04 出版日期:2014-11-15 发布日期:2014-11-15

Does progesterone show neuroprotective effects on traumatic brain injury through increasing phosphorylation of Akt in the hippocampus?

Richard Justin Garling 1, Lora Talley Watts 2, 3, 4, Shane Sprague 1, Lauren Fletcher 1, David F. Jimenez 1, Murat Digicaylioglu 1   

  1. 1 Department of Neurosurgery, University of Texas Health Science Center, San Antonio, TX, USA
    2 Research Imaging Institute, University of Texas Health Science Center, San Antonio, TX, USA
    3 Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, USA
    4 Department of Neurology, University of Texas Health Science Center, San Antonio, TX, USA
  • Received:2014-09-04 Online:2014-11-15 Published:2014-11-15
  • Contact: Lora Talley Watts, Ph.D., Research Imaging Institute, University of Texas Health Science Center at San Antonio, 8403 Floyd Curl Dr, San Antonio, TX 78229, USA, wattsl@uthscsa.edu.

摘要:

孕酮经PI3激酶通路增加Akt丝氨酸473位点磷酸化,从而增强Akt活性,对脑创伤起神经保护作用,但孕酮对苏氨酸308磷酸化位点的影响尚未见报道。实验旨在揭示孕酮是否可通过调节Akt苏氨酸308磷酸化位点调节Akt磷酸化水平,对海马起神经保护作用。免疫印迹检测结果显示,脑创伤后72h,大鼠海马Akt磷酸化水平明显下降,但经孕酮干预的脑创伤大鼠海马Akt磷酸化水平又明显升高。说明孕酮通过提高海马Akt磷酸化水平,对脑创伤起神经保护作用。

关键词: Akt, 脑创伤, 孕酮, 凋亡, 神经保护, 脑损伤, 免疫印迹, 控制性皮质撞击损伤

Abstract:

There are currently no federally approved neuroprotective agents to treat traumatic brain injury. Progesterone, a hydrophobic steroid hormone, has been shown in recent studies to exhibit neuroprotective effects in controlled cortical impact rat models. Akt is a protein kinase known to play a role in cell signaling pathways that reduce edema, inflammation, apoptosis, and promote cell growth in the brain. This study aims to determine if progesterone modulates the phosphorylation of Akt via its threonine 308 phosphorylation site. Phosphorylation at the threonine 308 site is one of several sites responsible for activating Akt and enabling the protein kinase to carry out its neuroprotective effects. To assess the effects of progesterone on Akt phosphorylation, C57BL/6 mice were treated with progesterone (8 mg/kg) at 1 (intraperitonally), 6, 24, and 48 hours (subcutaneously) post closed-skull traumatic brain injury. The hippocampus was harvested at 72 hours post injury and prepared for western blot analysis. Traumatic brain injury caused a significant decrease in Akt phosphorylation compared to sham operation. However, mice treated with progesterone following traumatic brain injury had an increase in phosphorylation of Akt compared to traumatic brain injury vehicle. Our findings suggest that progesterone is a viable treatment option for activating neuroprotective pathways after traumatic brain injury.

Key words: nerve regeneration, Akt, traumatic brain injury, progesterone, apoptosis, neuroprotection, brain injury, western blotting, controlled cortical impact, neural regeneration