长期低剂量离子辐射诱导小鼠皮层小胶质细胞中IL-1β表达异常升高的信号转导途径研究  

Signal transduction mechanism of abnormal IL-βupregulation in the mouse cortex under long time low-dose ionizing radiation

作　　者：后少俊 宋伦 Hou Shaojun;Song Lun(School of Basic Medical Sciences,Anhui Medical University,Hefei 230032,China;Institute of Military Cognition and Brain Science,Academy of Military Medical,Beijing 100850,China)

机构地区：[1]安徽医科大学基础医学院,合肥230032 [2]军事医学研究院军事认知与脑科学研究所,北京100850

出　　处：《河南师范大学学报（自然科学版）》2024年第5期134-141,I0012,共9页Journal of Henan Normal University(Natural Science Edition)

基　　金：国家自然科学基金(32070763);军队科技重点项目(XXX21X009).

摘　　要：低剂量离子辐射(low-doseionizingradiation,LDIR)的环境暴露对人体健康的影响已成为公共卫生研究领域备受关注的重要问题,但相应的分子机制研究进展缓慢.为探讨LDIR对脑功能的潜在危害效应及相关分子机制,采用8周龄雄性小鼠构建长期间歇性低剂量γ射线(Co60)暴露的实验动物模型,采用免疫荧光、WesternBlot、荧光定量PCR(qPCR)等技术,对辐射暴露后小鼠脑组织中的小胶质细胞活化状态、炎症因子表达水平和信号转导途径中蛋白激酶和转录因子的表达及活化水平进行分析.采用同剂量射线照射小胶质细胞N9并分析相应指标,用以模拟小胶质细胞的体内辐射反应状态.结果显示,LDIR暴露可诱导小鼠大脑皮层中小胶质细胞显著活化,并向M1型极化.以IL-1β为代表的神经炎症因子表达水平显著升高.N9细胞经低剂量γ射线暴露后IL-1β表达水平上调,其潜在调节因子c-Jun和ERKs的活化水平升高.敲低c-Jun的表达水平或抑制ERKs激酶活性后,IL-1β的诱导表达反应被显著抑制.实验结果表明,LDIR暴露可激活小胶质细胞并促进ERKs活化,进而激活转录因子c-Jun并介导IL-1β表达上调反应,这可能在LDIR诱发小鼠神经炎症反应发生发展中具有重要作用.The health hazard effects of Low-Dose Ionizing Radiation(LDIR)exposure have become an issue in the research area of public health,but the according mechanisms have not been clearly elucidated.To investigate the potentially harmful effects of long-term intermittent low-doseγ-radiation(Co 60)on the brain and the corresponding mechanisms involved,8-week-old male mice were exposed to such radiation to construct the experimental model.Immunofluorescence,Western Blot,and quantitative fluorescence PCR(qPCR)were used to examine the activation status of microglia,the expression level of inflammatory factors,and the expression and activation status of the protein kinase and the transcription factors involved in mediating the responses in the brain of mice after radiation exposure.The microglial cells N9 were subjected to the same dose of radiation to mimic the response of microglia in vivo under radiation.The findings indicate that LDIR exposure induced significant activation of microglia in the mouse cerebral cortex,which underwent polarization towards M1 type.Under the same conditions,the expression level of the neuroinflammatory factors,represented by IL-1β,was significantly increased after LDIR exposure.N9 cells exposed to low-doseγ-rays also showed a significantly increased expression of IL-βand the activation of its potential regulators,c-Jun and ERKs.Furthermore,knocking down the c-Jun expression or inhibiting ERKs activity significantly suppressed the induced expression of IL-1βin the LDIR-induced N9 cells.The experimental results demonstrate that LDIR exposure induced activation of the microglia,in which ERKs and c-Jun were sequentially activated to mediate the up-regulation of IL-βexpression.These responses might play an important role in the development of LDIR-induced neuroinflammation in mice.

关 键 词：低剂量离子辐射 小胶质细胞 神经炎症 IL-1Β 

分 类 号：Q691.5[生物学—生物物理学]