内源性脑源性神经生长因子在骨癌痛大鼠中的作用及其脊髓机制  

The role of brain-derived neurotrophic factor in pain facilitation and spinal mechanism in rat modelof bone cancer pain

作　　者：王丽娜[1] 杨建平[1] 嵇富海[1] 王秀云 左剑玲 许期年 贾晓明[1] 周静[1] 任春光[1] 李伟[1] 

机构地区：[1]苏州大学附属第一医院麻醉科,215006 [2]脑神经研究室

出　　处：《中华医学杂志》2011年第17期1188-1192,共5页National Medical Journal of China

基　　金：国家自然科学基金（30872442,81000479）;江苏省卫生厅基金（H200855）;江苏省卫生厅基金（H200917）;苏州市重大科技支撑计划项目（ZS0901）

摘　　要：目的探讨脑源性神经生长因子（BDNF）及其下游磷酸化细胞外信号调节蛋白激酶1／2（p-ERKl／2）在骨癌痛中的作用及其脊髓机制。方法雌性SD大鼠60只，随机分为5组（n=12），I组为模型对照组，Ⅱ组为骨癌痛组，Ⅲ组为模型对照组＋BDNF中和抗体，Ⅳ组为骨癌痛组＋IgG对照抗体；V组为骨癌痛组＋BDNF中和抗体。Ⅱ、Ⅳ和V组于大鼠左胫骨上端注人Walker256细胞，制备骨癌痛模型；模型对照组大鼠左胫骨上端注入Hank’S液。造模后第7—9天，Ⅲ、Ⅳ和V组鞘内分别注射BDNF中和抗体、IgG对照抗体和BDNF中和抗体15μg/10μl，1次／d，连续3d。分别于术前及术后隔日开始测定大鼠Von-Frey阈值，并测定脊髓后角的BDNF和p-ERKl／2表达水平。结果BDNF和P-ERKl／2在脊髓后角有共表达；术后第6-18天，与I组比较，Ⅱ、Ⅳ组Von-Frey阈值显著下降；术后第9天，脊髓BDNF和p-ERK1／2的蛋白表达显著增加（均P〈0．01）；Ⅲ组上述指标的差异无统计学意义（P〉0．05）；与Ⅱ、Ⅳ组比较，V组Von-Frey阈值显著增高，脊髓BDNF和P-ERKl／2的蛋白表达显著减少（均P〈0．01）。结论内源性BDNF可能通过其下游的p-ERKl／2信号转导途径参与了骨癌痛大鼠痛觉过敏的形成。Objective To investigate the role of brain-derived neurotrophic factor（BDNF） in pain facilitation and spinal mechanisms in the rat model of bone cancer pain. Methods The bone cancer pain model was developed by inoculated Walker 256 mammary gland carcinoma cells into the tibia medullary cavity. Sixty SD female rats were divided into 5 groups （n = 12 each） randomly; group I ：control group （ sham operation） ; group Ⅱ ： model group ; group Ⅲ ： control group ＋ anti-BDNF intrathecal （ i. t. ） ; group IV ： model group ＋ control IgG i. t. ; group V ： model group ＋ anti- BDNF i. t.. Anti-BDNF or control IgG was injected i. t. during 7 to 9th day. Von-Frey threshold was measured one day before operation and every 2 days after operation. On the 9th day after threshold tested, rats were sacrificed after i.t. injection of either antiBDNF or control IgG,the lumbar 4-6 spinal cord was removed. The expression of the spinal BDNF and the phosphorylation of extracellular signal-regulated protein kinasel/2 （p-ERK1/2） were detected by immunohistochemistry assay and Western-Blot. Co-expression pattern of BDNF and p-ERK1/2 were determined by double-labeling immunofluorescence. Results We demonstrated the coexistence of BDNF and p-ERK1/2 in the spinal cord of rats. From the 7 to 9th day after operation,von-Frey threshold in groups Ⅱ and IV was significantly lower than that in group I and group V （ P 〈 0. 01 ） , group V was remarkly higher than that in group Ⅳ（ P 〈 0.01 ）. The spinal BDNF and p-ERK1/2 expression in group Ⅱ or IV were significantly increased compared with that in group I or V （ P 〈 0. 01 ）, intrathecal anti-BDNF was significantly suppressed BDNF and p-ERK1/2 expression （ P 〈 0. O1 ）. Conclusion BDNF and p-ERK1/2was coexistence in the spinal cord of rats, and it maybe involved in the bone cancer pain.

关 键 词：骨肿瘤 疼痛 脑源性神经营养因子 脊髓 

分 类 号：R738.1[医药卫生—肿瘤]