鞘内注射慢病毒载体-SOCS3缓解骨癌痛大鼠痛行为及其机制  

Molecular mechanisms underlying the effect of intrathecal LV-SOCS3 injection on pain behaviors in a rat model of bone cancer

作　　者：孔祥鹏[1] 王迪煜 魏金荣[1] 杨志学[1] 陆向荣[2] 蒋国勤[1] KONG Xiang-peng WANG Di-yu WEI Jin-rong YANG Zhi-xue LU Xiang-rong JIANG Guo-qin(Department of Surgery, the Second Affiliated Hospital, Soochow University, Suzhou Jiangsu 215004 Department of Hand Surgery, the Affiliated Kunshan Hospital of Jiangsu University, Kunshan Jiangsu 215300, China)

机构地区：[1]苏州大学附属第二医院普外科,江苏苏州215004 [2]江苏大学附属昆山医院手外科,江苏苏州215300

出　　处：《江苏大学学报（医学版）》2017年第2期128-132,共5页Journal of Jiangsu University：Medicine Edition

基　　金：苏州市科教兴卫青年科技项目(KJXW2014011);苏州市科技计划项目(SYS201631);苏州大学附属第二医院优势临床学科团队资助项目(XKQ2015008)

摘　　要：目的:观察鞘内注射慢病毒(LV)过表达细胞因子信号转导抑制蛋白3(suppressor of cytokine signaling 3,SOCS3)对骨癌痛大鼠疼痛行为的影响并探讨其分子机制。方法:SD大鼠胫骨内注射乳腺癌Walker 256细胞建立骨癌痛模型,另以等体积生理盐水注射于大鼠胫骨内建立对照组。取12只造模1周的骨癌痛大鼠,6只鞘内注射LVSOCS3,另外6只鞘内注射LV-NC。应用行为学方法分别检测对照组、模型组、LV-SOCS3组及LV-NC组大鼠的机械性缩足反射阈值(PWT)、热刺激后爪退缩潜伏期(PWL)。蛋白质印迹法分别检测4组大鼠L_2-L_5背根神经节(dorsal root ganglion,DRG)中SOCS3、核转录因子(NF)-κB及P2X_3受体的表达。结果:骨癌大鼠表现出明显的机械痛敏和热痛敏,PWT和PWL显著降低;L2~L5DRG中SOCS3蛋白表达降低。鞘内注射LV-SOCS3后1周,骨癌大鼠的PWT和PWL值无明显变化,2周时PWT和PWL值明显升高(均P<0.05)。鞘内注射LV-SOCS3后1周,可上调SOCS3在L_2-L_5DRG中的表达,同时降低NF-κB的蛋白表达,但P2X_3受体表达无明显改变;鞘内注射LV-SOCS3后2周,可使NF-κB的表达维持低水平,同时降低了P2X_3受体的表达。结论:骨癌痛大鼠鞘内注射LV-SOCS3可通过调节NF-κB与P2X_3受体的表达缓解骨癌痛。Objective：To investigate the effects of suppressor of cytokine signaling 3（SOCS3） overexpression by intrathecal injection lentiviral（LV）-SOCS3 on the pain behaviors and potential mechanism in a rat model of bone cancer pain induced by breast cancer cells.Methods：Rats were injected with breast cancer cells to establish the models of bone cancer pain and control rats were injected with equal volume of normal saline（NS）.Six model rats were treated by intrathecal LV-SOCS3 injection,and the other six rats were treated by intrathecal injection of LV-NC after one week of cancer cells injection.The paw withdrawal latency（PWL） to thermal stimulation and paw withdrawal threshold（PWT） to von Frey filament stimulation were carried out on control group,bone cancer group,LV-SOCS3 group and LV-NC group.Western blotting was performed to detect changes of SOCS3,NF-κB and P2X_3receptors（P2X_3R） at protein levels in L_2-L_5 dorsal root ganglion（DRGs） in different groups.Results：All rats presented enhanced mechanical and thermal hyperalgesia after intra-tibial injection of breast cancer cells,whose PWT and PWL were lower than those of control group.The protein level of SOCS3 was obviously reduced in bone cancer group.The PWT and PWL were higher than those of LV-NC group at two weeks after intrathecal injection of LV-SOCS3 butnot at the time of one week after injection.SOCS3 could be significantly increased and NF-κB reduced in L_2-L_5 DRGs at one week after intrathecal LV-SOCS3 injection,but no change in P2X_3 R protein level was observed.At two weeks after intrathecal injection of LV-SOCS3,the protein level of NF-κB was maintained at low level and P2X_3 R protein level was also significantly reduced.Conclusion：Intrathecal injection of LV-SOCS3 could modulate the expression of NF-κB and P2X_3 R in bone cancer pain rats,which resulted in attenuation of bone cancer pain.

关 键 词：骨癌痛 细胞因子信号转导抑制蛋白3 P2X3受体 核因子-κB 

分 类 号：R730.54[医药卫生—肿瘤]