SDF-1/CXCR4信号通路对骨癌痛大鼠脊髓背角FOS蛋白表达的影响  

Effects of SDF-1/CXCR4 Signal Pathway on FOS Protein Expression in Spinal Dorsal Horn of Rats with Bone Induced Cancer Pain

作　　者：王安平[1] 岳新霞[2] 常琦[2] 王龙[1] 海力茜.陶尔大洪 WANG Anping;YUE Xinxia;CHANG Qi;WANG Long;HAILIQIAN Taoerdahong(The Second Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang,830000,China;Xinjiang Autonomous Region People’s Hospital North Campus,Urumqi,Xinjiang,830000,China;College of Pharmacy,Xinjiang Medical University,Urumqi,Xinjiang,830054,China)

机构地区：[1]新疆医科大学第二附属医院,新疆乌鲁木齐830000 [2]新疆自治区人民医院北院,新疆乌鲁木齐830000 [3]新疆医科大学药学院,新疆乌鲁木齐830054

出　　处：《肿瘤药学》2018年第3期329-332,共4页Anti-Tumor Pharmacy

摘　　要：目的观察SDF-1/CXCR4信号通路对骨癌痛(cancer induced bone pain,CIBP)大鼠脊髓背角FOS蛋白表达的影响。方法 40只健康雌性SD大鼠随机分成5组:Normal组,Sham-Veh组,Sham-AMD3465组,CIBP-Veh组及CIBPAMD3465组。第4、5组大鼠胫骨内注射Walker肿瘤细胞(乳腺癌细胞)构建骨癌痛模型;第2、3、4和5组术后第1 d至术后第14 d连续给予AMD3465(CXCR4一种选择性拮抗剂)/Veh;术前第1 d至术后第14 d采用Von-Frey机械细丝连续观察大鼠的术侧后足痛阈改变;免疫荧光双重标记法观察SDF-1/CXCR4在脊髓背角的细胞分布;Western blot定量检测脊髓背角SDF-1与CXCR4蛋白的表达水平;免疫组织化学染色法观察脊髓背角FOS阳性细胞表达数。结果术后第1 d至7 d,大鼠术侧后足的机械痛阈缓慢降低,在术后第7 d降至最低,第7 d至第14 d痛阈维持在较低水平,给予CXCR4选择性拮抗剂AMD3465后大鼠术侧痛阈明显上升。SDF-1和CXCR4表达在神经元上,Western blot检测结果进一步说明CIBP模型大鼠脊髓背角内SDF-1和CXCR4的表达明显增加(P<0.05),给予CXCR4选择性拮抗剂AMD3465后,SDF-1和CXCR4蛋白的显著降低(P<0.05);CXCR4选择性拮抗剂AMD3465能够有效降低FOS阳性细胞的数量。结论 SDF-1/CXCR4信号通路参与骨癌痛的发生发展,并可调控脊髓背角内FOS蛋白的表达。Objective To observe the effect of SDF-1/CXCR4 signaling pathway on the expression of FOS protein in the spinal dorsal horn of rats with bone cancer pain.Method Forty healthy female SD rats were randomly divided into five groups:Normal group,Sham-Veh group,Sham-AMD3465 group,CIBP-Veh group and CIBP-AMD3465 group.Rats in groups 4 and 5 were injected with Walker tumor cells(breast cancer cells)in the tibia to construct a bone cancer pain model.Rats in groups 2,3,4 and 5 were continuously given AMD3465(CXCR4 selective antagonist)/Veh from the 1st day to the 14th day after operation.The pain threshold of the hindfoot of rats was continuously observed by Von-Frey mechanical filaments from the 1st day to the 14th day after operation.The cell distribution of SDF-1/CXCR4 in the dorsal horn of spinal cord was observed by immunofluorescence double labeling.Western blot was used to quantitatively detect the expression of SDF-1 and CXCR4 in dorsal horn of spinal cord.Immunohistochemical staining was used to observe the expression of FOS positive cells in dorsal horn of spinal cord.Results The mechanical threshold of the hind paw of the rat was gradually reduced from the first postoperative day to the seventh postoperative day,and it was the lowest at the 7th postoperative day.The pain threshold was maintained at a low level from the 7th to the 14th postoperative day.At the level,the side pain threshold increased significantly after administration of CXCR4 selective antagonist AMD3465.The SDF-1 and CXCR4 were expressed on neurons.Western blot results further demonstrated that the expressions of SDF-1 and CXCR4 increased significantly in the spinal dorsal horn of CIBP rats(P<0.05).After administration of CXCR4 selectiveantagonist AMD3465,the SDF-1 and CXCR4 proteins were significantly decreased(P<0.05).CXCR4 selectivity antagonist AMD3465 can effectively reduce the number of FOS-positive cells.Conclusion SDF-1/CXCR4 signaling pathway was involved in the occurrence and development of bone cancer pain,and it could regulate the e

关 键 词：SDF-1 CXCR4 信号通路 骨癌痛 FOS 

分 类 号：R730.6[医药卫生—肿瘤]