Radiation and microgravity exert different biological effects on the human brain during space flight. Studies rarely focus on the two combined. The central nervous system (CNS) is among the most crucial systems in the human brain. Inflammatory activation of glial cells is the principal sign of damage to nerve function. Therefore, the present study established in vitro models of radiation, simulated microgravity, and a combination of the two, in order to explore the resultant biological changes occurring in human glial cells. Experiments were performed on U-87 MG cells to study the release of inflammatory factors, changes in autophagy, and the transcription level of a key regulatory factor of histone methyltransferase enhancer of zeste 2 (EZH2). The results demonstrated that a simulated space environment significantly impacted cell growth and morphology. Neurons released cytokines that recruited monocytes, invoking an inflammatory response. Both radiation and microgravity activated cell autophagy. Finally, the meta-transcriptomics of glial cells were comprehensively analyzed, focusing on changes in the transcription of genes regulating autophagy. The results indicated that transcription levels of EZH2, the critical dual regulator of inflammation and autophagy, decreased in a simulated space environment, suggesting that U-87 MG cells inhibit EZH2 expression in such conditions. The down-regulation of EZH2 induced autophagy through activation of the mTOR pathway. Changes in levels of autophagy activated NF-κB and induced the release of the inflammatory factor IL-6. The interaction between NF-κB and EZH2 may also, in turn, affect the expression of EZH2, creating a U-87 MG cell inflammatory activation cycle. In summary, the results indicate that EZH2 may be a dual-regulator of inflammatory activation and autophagy in a simulated space environment, helping to explain the biological damage observed in the CNS in a space environment due to neuroinflammation, providing molecular targets for the health protection of astronauts during long-term space flight.

在太空飞行过程中，辐射和微重力对人脑产生不同的生物效应。研究很少关注两者的结合。中枢神经系统 (CNS) 是人类大脑中最重要的系统之一。神经胶质细胞的炎症激活是神经功能受损的主要标志。因此，本研究在体外建立辐射模型、模拟微重力模型以及两者的结合，以探索人类神经胶质细胞中发生的由此产生的生物学变化。对 U-87 MG 细胞进行了实验，以研究炎症因子的释放、自噬的变化以及 zeste 2 (EZH2) 组蛋白甲基转移酶增强子的关键调节因子的转录水平。结果表明，模拟的空间环境显着影响了细胞的生长和形态。神经元释放招募单核细胞的细胞因子，引发炎症反应。辐射和微重力均激活细胞自噬。最后，对神经胶质细胞的宏转录组学进行了综合分析，重点关注调控自噬的基因转录的变化。结果表明，EZH2、炎症和自噬的关键双重调节剂在模拟空间环境中降低，表明 U-87 MG 细胞在这种条件下抑制 EZH2 表达。EZH2 的下调通过激活 mTOR 通路诱导自噬。自噬水平的变化激活 NF-κB 并诱导炎症因子 IL-6 的释放。NF-κB 和 EZH2 之间的相互作用也可能反过来影响 EZH2 的表达，从而产生 U-87 MG 细胞炎症激活周期。总之，结果表明 EZH2 可能是模拟空间环境中炎症激活和自噬的双重调节剂，有助于解释在空间环境中由于神经炎症在中枢神经系统中观察到的生物损伤，