microRNA在模拟空间辐射环境诱导星形胶质细胞促增殖旁效应中的作用研究

Role of microRNA in Bystander Effect of Astrocyte Proliferation Induced by Simulated Space Radiation

  • 摘要: 星形胶质细胞是中枢神经系统中最常见的细胞类型,也是辐射敏感的细胞类型之一。辐射不仅会影响星形胶质细胞自身的生长,还会通过细胞旁效应影响周围的神经细胞,进而诱导中枢神经系统的损伤。本研究利用60Co产生的γ射线和12C6+产生的重离子射线,分别以耐受剂量(2 Gy的γ射线和0.2 Gy的重离子射线)和半致死剂量(10 Gy的γ射线和2 Gy的重离子射线)辐照人脑星形胶质母细胞瘤细胞(U-87 细胞),比较两种射线对细胞存活率和旁细胞的影响。结果表明,γ射线和重离子射线在两种剂量下对细胞存活率和旁细胞增殖的影响有显著差异,其中γ射线诱导星形胶质细胞促增殖的旁效应,而重离子射线诱导抑制增殖的旁效应。进一步使用RNA高通量测序技术和生物信息学分析辐照前后细胞外培养基中外泌体内microRNA的表达差异情况,发现3种与细胞增殖相关的microRNA,分别是miR-24-1-5p、miR-100-5p和miR-7704,它们能够通过不同的机制共同调节旁细胞的增殖。此外,还检测了γ射线和重离子射线对这3种microRNA在细胞内外分布的影响,发现γ射线和重离子射线在不同剂量下对3种microRNA的表达影响不同。本研究发现的这3种microRNA可能是辐射诱导的星形胶质细胞促增殖旁效应的一个重要靶点,能够为揭示辐射诱导的神经致炎性细胞损伤旁效应的分子作用机制提供新的线索和思路。

     

    Abstract: Astrocytes, the most common cell type in the central nervous system, are particularly sensitive to ionizing radiation. Beyond affecting astrocyte growth, ionizing radiation also exerts bystander effects on neighboring neural cells, leading to damage within the central nervous system. The space environment is inundated with radiation, including solar particle radiation primarily composed of protons and galactic cosmic rays consisting of high-energy protons, heavy ions, and γ-rays. Space radiation represents one of the most significant health risks faced by astronauts during spaceflight missions. To address this, the γ-rays generated by 60Co and heavy ion radiation produced by 12C6+ were employed in this paper. Human brain astrocytoma cells (U-87 cells) were irradiated at varying gradients of doses to explore the tolerance dose corresponding to an 80% cell survival rate and the semi-lethal dose corresponding to a 50% cell survival rate. Subsequently, tolerance doses (2 Gy of γ-rays and 0.2 Gy of heavy ion radiation) and semi-lethal doses (10 Gy of γ-rays and 2 Gy of heavy ion radiation) were administered to U-87 cells to compare the effects of these two types of radiation on bystander cell proliferation in U-87 cells. The results reveal significant differences in cell survival and bystander cell proliferation between γ-rays and heavy ion radiation at both dose levels. Specifically, γ-rays induce a proliferation-promoting bystander effect in astrocytes, while heavy ion radiation lead to a proliferation-inhibiting bystander effect. This suggests that the cellular response to radiation is not uniform and can vary significantly depending on the type and intensity of the exposure. Three proliferation-related microRNAs, namely miR-24-1-5p, miR-100-5p, and miR-7704, were identified through further investigation using RNA high-throughput sequencing technology and bioinformatics analysis. These microRNAs collectively regulate bystander cell proliferation through distinct mechanisms. Additionally, the effect of different radiation types on the intracellular and extracellular distribution of these three microRNAs was assessed. Notably, γ-rays and heavy ion radiation exhibit differential effects on the expression of these microRNAs at varying doses, corresponding to different mechanisms within the cells. The intricate interplay between these microRNAs and their target genes could be pivotal in mediating the cellular response to radiation-induced stress. The above research results indicate the importance of developing targeted protective strategies to mitigate the adverse effects of space radiation on the health of astronauts, particularly focusing on the central nervous system.

     

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