NR1磷酸化在神经生长因子加剧大鼠骨癌痛中的作用  

Roles of NMDA Receptor NRl Subunit Phosphorylation on Nerve Growth Factor-facilitated Bone Cancer Pain in Rats

作　　者：姚鹏[1] 丁远远[1] 马佳明[1] 蒋晶晶[2] 张锦[2] 孟凌新[1] 

机构地区：[1]中国医科大学附属盛京医院疼痛科,沈阳110004 [2]中国医科大学附属盛京医院麻醉科,沈阳110004

出　　处：《中国医科大学学报》2011年第2期117-121,共5页Journal of China Medical University

基　　金：辽宁省自然科学基金资助项目(20082111)

摘　　要：目的探讨骨癌痛大鼠背根神经节(DRG)神经生长因子(NGF)表达及NR1磷酸化情况,并观察鞘内注射神经生长因子抗体(anti-NGF)对NR1磷酸化及骨癌痛大鼠疼痛行为的影响。方法检测骨癌痛大鼠DRG NGF的表达及NR1磷酸化:雌性SD大鼠随机分成假手术(sham)组及cancer组,每组10只,分别在左胫骨注射PBS液或walker256瘤细胞,21 d取左侧L4-5DRG。检测anti-NGF对NR1磷酸化及大鼠疼痛行为的影响:骨癌痛大鼠鞘内置管,随机分成生理盐水(NS)组及anti-NGF组,于接种瘤细胞16 d开始分别鞘内注射生理盐水或anti-NGF。于接种瘤细胞前、接种后13、18及21 d进行疼痛行为测试,接种21d取大鼠左侧L4-5DRG,Western blot方法检测NR1磷酸化。结果与sham组比较c,ancer组大鼠DRG NGF表达显著上调,NR1磷酸化水平增加(P<0.01)。鞘内注射anti-NGF后,与NS组比较,机械痛阈降低和热辐射潜伏期延长。NS组NR1磷酸化水平高于anti-NGF组(P<0.05)。结论 anti-NGF减弱骨癌痛、抑制NR1磷酸化,提示NGF通过NR1磷酸化加剧大鼠骨癌痛。Objective To evaluate the expression of nerve growth factor（NGF） and NMDA receptor NR1 subunit phosphorylation and investigate the effects of anti-NGF on dorsal root ganglion（DRG） NR1 phosphorylation and pain in the rats with bone cancer pain.Methods Twenty rats were randomly divided into sham and cancer group（n =10 per group） by inoculating PBS or walker256 cancer cell solution into the left tibia.On day 21,the left lumbar 4-5 DRG were removed for detecting the expression of NGF and phosphorylated NR1 with Western blot.Cancer rats,in which the intrathecal catheter were surgically implanted,were randomly assigned to NS and anti-NGF group（n =10 per group）.Intrathecal injection of saline or anti-NGF was given from day 16 to 21 after inoculation.Mechanical and thermal hyperalgesia was assessed before inoculation（baseline）,on day 13,18 and 21 after inoculation.After the behavioral test on day 21,the left lumbar 4-5 DRG were removed to measure phosphorylated NR1 with Western blot.Results The expression of NGF and the levels of phosphorylated NR1 were significantly up-regulated in the DRG of the cancer group rats compared with those of sham group.Intrathecal injection of anti-NGF attenuated the mechanical and thermal hyperalgesia compared with the rats of group NS,a reduced tendency in paw withdrawal latency（PWL） and a decreased paw withdrawal threshold（PWT） were observed in anti-NGF group rats.Phosphorylated NR1 levels were significantly higher in NS group rats than anti-NGF group rats,which indicated that anti-NGF inhibited DRG NR1 phosphorylation during bone cancer pain.Conclusion Anti-NGF might attenuate bone cancer pain and inhibit NR1 phosphorylation,which indicated that NGF could enhance NR1 phosphorylation to facilitate bone cancer pain.

关 键 词：神经生长因子 N-甲基-D-天冬氨酸受体 磷酸化 骨癌痛 

分 类 号：R738[医药卫生—肿瘤]