中国神经再生研究(英文版) ›› 2016, Vol. 11 ›› Issue (3): 476-479.doi: 10.4103/1673-5374.179066

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

丙咪嗪能通过TrkB信号通路抑制视网膜神经节细胞凋亡

  

  • 收稿日期:2016-01-18 出版日期:2016-03-15 发布日期:2016-03-15

Imipramine protects retinal ganglion cells from oxidative stress through the tyrosine kinase receptor B signaling pathway

Ming-lei Han, Guo-hua Liu, Jin Guo, Shu-juan Yu, Jing Huang   

  1. Department of Ophthalmology, Qilu Children Hospital, Shandong University, Jinan, Shandong Province, China
  • Received:2016-01-18 Online:2016-03-15 Published:2016-03-15
  • Contact: Ming-lei Han, M.D.,Dick_han@aol.com.

摘要:

三环类抗抑郁药丙咪嗪可在多种神经系统中刺激脑源性神经营养因子/TrkB通路,是否也对视网膜神经节细胞也能发挥这种神经保护作用尚不清楚。为此实验在使用H2O2损伤体外培养的视网膜神经节细胞30min前以丙咪嗪预处理。Western blot结果发现,丙咪嗪可促进损伤细胞中ERK和TrkB的磷酸化,激活TrkB通路;TUNEL染色也证实丙咪嗪抑制了H2O2诱导的细胞凋亡。而丙咪嗪干预后1.5h以TrkB抗体干预,则能阻止丙咪嗪对凋亡的抑制作用。由此说明丙咪嗪通过TrkB信号通路产生了保护视网膜神经节细胞的效应。

关键词: 神经再生, 视网膜神经节细胞, 丙咪嗪, 氧化应激, 细胞凋亡, TrkB

Abstract:

Retinal ganglion cell (RGC) degeneration is irreversible in glaucoma and tyrosine kinase receptor B (TrkB)-associated signaling pathways have been implicated in the process. In this study, we attempted to examine whether imipramine, a tricyclic antidepressant, may protect hydrogen peroxide (H2O2)-induced RGC degeneration through the activation of the TrkB pathway in RGC-5 cell lines. RGC-5 cell lines were pre-treated with imipramine 30 minutes before exposure to H2O2. Western blot assay showed that in H2O2-damaged RGC-5 cells, imipramine activated TrkB pathways through extracellular signal-regulated protein kinase/TrkB phosphorylation. TUNEL staining assay also demonstrated that imipramine ameliorated H2O2-induced apoptosis in RGC-5 cells. Finally, TrkB-IgG intervention was able to reverse the protective effect of imipramine on H2O2-induced RGC-5 apoptosis. Imipramine therefore protects RGCs from oxidative stress-induced apoptosis through the TrkB signaling pathway.

Key words: nerve regeneration, retinal ganglion cell, imipramine, oxidative stress, apoptosis, tyrosine kinase receptor B, neural regeneration