鞘内注射miR-16模拟物对骨癌痛大鼠行为及其靶基因BDNF表达的影响  

Effects of miR-16 mimics on the pain behavior and the expression of its target gene BDNF in rats with bone cancer pain

作　　者：张婷[1] 曹守彬 范后宝 申文[3] 

机构地区：[1]徐州市中心医院疼痛科,徐州221002 [2]江苏省麻醉与镇痛应用技术重点实验室 [3]徐州医学院附属医院疼痛科

出　　处：《中华行为医学与脑科学杂志》2015年第11期978-981,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：江苏省健康专项基金（BE2015626）

摘　　要：目的 探讨miR-16在骨癌痛大鼠脊髓中表达量的变化规律及鞘内注射miR-16模拟物（miR-16 mimics）对骨癌痛大鼠行为学及其靶基因BDNF表达的影响.方法 在大鼠右侧胫骨骨髓腔注入Walker 256乳腺癌细胞建立骨癌痛模型后,采用real-time PCR的方法检测假手术组（S组）和骨癌痛组（BCP组）造模前1d,造模后3,5,7,10和14 d脊髓miR-16的表达量变化;在造模后10d,11d,12d,BM组大鼠鞘内注射miR-16 mimics,BN组鞘内注射对照序列,检测大鼠行为学变化,造模后14 d测完行为学处死大鼠检测脊髓BDNF的表达变化.结果 与S组和基础值相比,骨癌痛组大鼠术后5d～14d脊髓水平miR-16的表达量呈时间依赖性下调,5 d（0.91±0.04）,7 d（0.77±0.01）,10 d（0.73±0.03）,14 d（0.42±0.08）,（均P＜0.05）;造模后14 d,miR-16靶基因BDNF在BN和BP组大鼠脊髓中的表达量明显升高（2.78±0.31）（2.34±0.23）（均P＜0.01）,而鞘内注射miR-16 mimics可明显降低骨癌痛大鼠的机械痛阈及其脊髓水平BDNF的表达（1.42±0.16）（P＜0.01）.结论 miR-16在骨癌痛大鼠脊髓水平表达呈时间依赖性下调,鞘内注射miR-16的模拟物能够缓解骨癌.Objective To investigate the expression of miR-16 in spinal cord and the effects of miR-16 mimics on the pain behavior and the expression of its target gene BDNF during the development and maintenance of bone cancer pain.Methods The bone cancer pain model rats were developed by intra-tibia inoculation of Walker 256 mammary gland cells.Before inoculation and 3,5,7,10,14 d after inoculation,the samples of spinal cord L4～6 lumbar enlargement were collected to detect the expression of miR-16 using real-time PCR.Mice in group BM and group BN were intrathcal injected of miR-16 mimics and its negative control products on 10 d,11 d,12 d after inoculation.Paw withdrawal mechanical threshold （PWMT） was measured using von Frey hair mechanical stimulation.The expression of BDNF was detected using western-blot on 14 d after behavior tests.Results Compared with the base level and the level in group S,the significant decrease of miR-16 expression was observed at 5 d～14dingroupT （5d （0.91±0.04）,7 d （0.77±0.01）,10 d （0.73±0.03）,14d （0.42±0.08）） （all P〈 0.05）.Compared with SH group,PWMT was significantly decreased in BC and BP groups at 5 d～ 14 d （P〈0.05）,and in group BM at 5 d～ 10 d（P〈0.05）.Compared with BP group,PWMT was significantly higher in BM group at 10～12 d（P〈0.05）.Compared with SH group,the expression of BDNF was significantly increased in BN and BP groups（（2.78±0.31）,（2.34±0.23）） （all P〈0.01）.Compared with BP group,the expression of BDNF was significantly decreased in BM group （1.42±0.16） （P〈0.01）.Conclusion miR-16 is downregulated in spinal cord of bone cancer pain rats,while intrathcal injection of miR-16 mimics can attenuate the pain behaviors in a rat model of bone cancer pain and decrease the expression of BDNF.miR-16 may modulate bone cancer pain through BDNF.

关 键 词：骨癌痛 脊髓 miR-16 miR-16模拟物 脑源性神经营养因子 

分 类 号：R738.1[医药卫生—肿瘤]