大鼠骨癌痛模型中脊髓背角神经元与星型胶质细胞相互联系的研究  

Crosstalk between spinal neurons and astrocytes in bone cancer pain in rats

作　　者：郭池华 刘焕 赵妍 王爽 郭玉芳 王湘 霍健 徐浩 GUO Chihua;LIU Huan;ZHAO Yan;WANG Shuang;GUO Yufang;WANG Xiang;HUO Jian;XU Hao(School of Basic Medical Sciences,Xi'an Medical University,Shanxi Xi'an 710021,China.)

机构地区：[1]西安医学院基础医学部,陕西西安710021

出　　处：《现代肿瘤医学》2020年第23期4027-4032,共6页Journal of Modern Oncology

基　　金：国家自然科学基金项目(编号:81803099)。

摘　　要：目的:研究大鼠骨癌痛模型中脊髓背角神经元与星型胶质细胞相互联系。方法:利用Walker256乳腺癌细胞建立大鼠骨癌痛模型后,分别鞘内注射药物阻断神经元的活化(c-Fos反义寡核苷酸探针,c-Fos ASO)和星形胶质细胞的活化(L-α-aminoadipate,L-α-AA),然后分别检测大鼠痛行为学改变;利用免疫荧光染色法和Western blot实验检测大鼠脊髓背角神经元活化标记物c-Fos和星形胶质细胞标记物GFAP的表达变化。结果:骨癌痛大鼠出现了显著的痛行为学改变并激活了脊髓背角神经元和星形胶质细胞,表现为早期c-Fos和晚期GFAP的表达增加。鞘内注射c-Fos ASO或L-α-AA均有明显镇痛效果。免疫荧光染色提示c-Fos ASO不仅能显著抑制骨癌痛大鼠神经元的活化,而且对星形胶质细胞的活化也有抑制作用。与此同时,Western blot显示L-α-AA不但抑制了星形胶质细胞的活化,也缩短了神经元的活化时间。结论:神经元和星形胶质细胞相互联系伴随着骨癌痛的发生发展。因此,研究新的镇痛策略,应综合考虑两者的协调关系。Objective:To investigate the effect of the crosstalk between spinal neurons and astrocytes on pain behavior in rats model of bone cancer pain(BCP).Methods:BCP model was developed by Walker 256 mammary gland carcinoma cells.In order to test of pain behavior changes in rats,intrathecal administration of neuronal c-Fos antisense oligodeoxynucleotides(ASO)or astroglial toxin L-α-aminoadipate(L-α-AA)were used,respectively.Expression of spinal c-Fos was detected by immunofluorescence staining.Western blot analysis was used to detect expression changes of spinal GFAP.Results:Significant pain behavior changes were detected in bone cancer pain rats with the activated spinal neurons stained by the c-Fos expression at the early phase and the activated astrocytes stained by GFAP during the late phase of pain.Intrathecal administration of neuronal c-Fos ASO or astroglial L-α-AA reversed the allodynia in BCP rats.Immunofluorescence staining revealed that c-Fos ASO significantly not only inhibited the activation of neurons but also astrocytes.Meanwhile,Western blot analysis exhibited that L-α-AA not only suppressed the activation of astrocytes,but also shortened the time of neuronal activation.Conclusion:The neuronal and astrocytic activations and their"crosstalk"maintain BCP in rats.Therefore,these"crosstalk"should considered when we make some novel analgesic strategies in future.

关 键 词：骨癌痛 神经元 星形胶质细胞 镇痛 

分 类 号：R738.1[医药卫生—肿瘤]