BDNF/TrkB通路活化星形胶质细胞对大鼠神经病理性痛的影响

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1h测定50％机械缩爪阈值(50％ PWT);末次给药后1h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.

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

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.