上海交通大学学报（医学版）

›› 2012, Vol. 32 ›› Issue (3): 279-.doi: 10.3969/j.issn.1674-8115.2012.03.009

• 论著（基础研究） • 上一篇    下一篇

BDNF/TrkB通路活化星形胶质细胞对大鼠神经病理性痛的影响

汪 静1,2, 张 昕1, 江 伟2, 杜冬萍1   

  1. 上海交通大学附属第六人民医院 1.疼痛科, 2.麻醉科, 上海 200233
  • 出版日期:2012-03-28 发布日期:2012-03-28
  • 通讯作者: 杜冬萍, 电子信箱: dudp@sjtu.edu.cn。
  • 作者简介:汪 静（1986—）, 女, 硕士生；电子信箱: wang_xjq0521@163.com。

Contribution of BDNF/TrkB pathway to development of neuropathic pain by activation of astrocytes in rats

WANG Jing1,2, ZHANG Xin1, JIANG Wei2, DU Dong-ping1   

  1. 1.Pain Management Center, 2.Department of Anesthesiology, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China
  • Online:2012-03-28 Published:2012-03-28

PDF (PC)

1258

摘要：

目的 观察外源性脑源性神经营养因子（BDNF）对大鼠机械痛阈和星形胶质细胞的影响，探讨BDNF参与疼痛调控的可能机制。方法 将30只鞘内置管成功的大鼠随机分为空白对照组、安慰剂组、BDNF组、BDNF+星形胶质细胞抑制剂组（BDNF+氟代柠檬酸组）及BDNF+酪氨酸激酶受体B（TrkB）抑制剂组（BDNF+K252a组），每组6只。予鞘内注入药物，1次/d×7 d。每次注药前1 h测定50%机械缩爪阈值（50%PWT）；末次给药后1 h取脊髓腰膨大，Western blotting法测定胶质细胞纤丝酸性蛋白（GFAP）及磷酸化TrkB的蛋白表达。结果 BDNF组大鼠后肢50%PWT较空白对照组显著下降（P<0.05）；给药后第7天，BDNF组大鼠脊髓腰膨大GFAP和磷酸化TrkB的蛋白表达较空白对照组显著升高（P<0.01）。BDNF+氟代柠檬酸组和BDNF+K252a组50%PWT和GFAP蛋白表达水平与空白对照组比较，差异无统计学意义（P>0.05）。BDNF+K252a组磷酸化TrkB的蛋白表达与空白对照组比较，差异无统计学意义（P>0.05）。结论 BDNF可能通过磷酸化TrkB受体使脊髓星形胶质细胞活化，进而参与神经病理性痛的发生和发展过程。

关键词: 脑源性神经营养因子, 胶质细胞纤丝酸性蛋白, 神经病理性痛, 磷酸化酪氨酸激酶受体B, 氟代柠檬酸, K252a

Abstract:

Objective To investigate the effects of exogenous brain-derived neurotrophic factor (BDNF) on mechanical pain threshold and astrocytes, and explore the potential mechanism of BDNF-induced pain. Methods Thirty rats with successful intrathecal catheterization were randomly divided into blank control group, placebo group, BDNF group, BDNF+astrocyte inhibitor group (BDNF+fluorocitrate group) and BDNF+tyrosine kinase receptor B(TrkB) inhibitor group (BDNF+K252a group), with 6 rats in each group. Intrathecal administration was performed once daily for 7 d. Fifty percent paw withdrawal threshold (50% PWT) was measured 1 h before each injection. Spinal enlargement parts were obtained 1 h after the last administration, and the expression of glial fibrillary acidic protein (GFAP) and phosphorylated TrkB protein was detected by Western blotting. Results Compared with blank control group, 50% PWT of hind limbs in BDNF group was significantly lower (P<0.05). Seven days after administration, the expression of GFAP and phosphorylated TrkB protein in spinal enlargement parts in BDNF group was significantly higher than that in blank control group (P<0.01). The expression of GFAP protein and 50% PWT in BDNF+ fluorocitrate group and BDNF+K252a group were not significantly different from those in blank control group (P>0.05). There was no significant difference in the expression of phosphorylated TrkB protein between BDNF+K252a group and blank control group (P>0.05). Conclusion BDNF may activate astrocytes via phosphorylated TrkB receptor, which in turn produce neuropathic pain.

Key words: brain-derived neurotrophic factor, glial fibrillary acidic protein, neuropathic pain, phosphorylated tyrosine kinase receptor B, fluorocitrate, K252a