论文部分内容阅读
目的研究骨癌痛大鼠脊髓背角钾离子-氯离子联合转运体2(potassium-chloride cotransporter2,KCC2)的表达变化及其可能机制。方法采用大鼠胫骨骨髓腔接种Walker256肿瘤细胞建立胫骨癌痛模型。观测种瘤前后大鼠机械缩足反射阈值(mechanical withdrawl thresthold,MWT)和脊髓背角KCC2表达水平的变化,观察痛敏形成前鞘内预注射酪氨酸蛋白激酶B(tyrosine protein kinase B,TrkB)中和抗体阻断脑源性神经营养因子(brain-derived neurotrophic factor,BD-NF)-TrkB途径对KCC2表达和机械性痛觉超敏的影响。结果大鼠种瘤后6～12d,MWT明显下降(P<0.01),出现明显的机械性痛敏,脊髓背角KCC2蛋白水平进行性降低(P<0.01);鞘内预注射TrkB中和抗体的骨癌痛大鼠,其脊髓KCC2表达水平和MWT明显高于注射IgG和不作处理的骨癌痛大鼠(P<0.01)。结论脊髓背角的KCC2可能参与了骨癌痛的发生发展,而BDNF-TrkB途径可能介导了该作用。
Objective To study the expression changes of potassium-chloride cotransporter2 (KCC2) in spinal dorsal horn and its possible mechanism in bone cancer pain rats. Methods Walker256 tumor cells were inoculated into rat tibia medullary cavity to establish a model of tibial cancer pain. The changes of mechanical withdrawl thresthold (MWT) and KCC2 expression in spinal dorsal horn were observed before and after germ plasm. The levels of tyrosine protein kinase B (TrkB) ) Neutralizing antibodies to block the expression of brain-derived neurotrophic factor (BD-NF) -TrkB pathway on KCC2 expression and mechanical hyperalgesia. Results MWT was significantly decreased (P <0.01) on 6-12 days after tumor implantation in rats, and significant mechanical pain sensation was found. The KCC2 protein level in spinal dorsal horn was decreased (P <0.01), while intrathecal pretreatment with TrkB neutralizing antibody (P <0.01). The expression level of KCC2 and MWT in spinal cord of rats with bone cancer pain were significantly higher than those of injected pain and untreated bone cancer rats (P <0.01). Conclusion KCC2 in spinal dorsal horn may be involved in the development of bone cancer pain, and BDNF-TrkB pathway may mediate this effect.