摘要目的:揭示束流时间结构与组织氧含量对自由基动力学的耦合作用机制，进而解释FLASH效应的潜在生物学基础，并为FLASH放疗的束流优化和计划设计提供参考。方法:使用TOPAS-nBio v3.0模拟电子束在水中产生的物理与化学作用过程，建立涵盖羟基自由基(·OH)和水合电子(e aq-)等自由基生成、扩散、反应与猝灭的全尺度动力学模型。在不同束流时间结构(单脉冲、多脉冲、连续波照射)及不同氧浓度条件下，系统模拟自由基演化动态。同时，通过实验测试激光吸收光谱获取e aq-含量数据，验证模型预测的准确性。 结果:实验测得的e aq-浓度变化趋势与模拟结果高度一致，验证了所构建模型的可靠性。束流时间结构对自由基浓度峰值与持续时间具有显著影响，单脉冲结构可导致自由基短时间内快速升高后迅速猝灭，而连续或长脉冲结构则引起自由基浓度在较长时间内维持较高水平。·OH的演变对氧环境不敏感，而e aq-则受氧环境影响剧烈。低氧环境下e aq-自由基清除效率明显下降，导致生物大分子的氧化损伤累积增强。富氧环境下e aq-寿命快速缩短。 结论:自由基动力学受到束流时间结构和氧含量的双重调控。FLASH放疗可以利用单脉冲或多脉冲间隙期形成周期性窗口，正常组织通过高效抗氧化清除自由基降低损伤，而肿瘤组织中自由基持续累积并放大损伤，从而产生选择性保护效应。

abstractsObjective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.