在斑块形成中,香烟烟雾中介氧化应激的不利结局途径
Patrudu Makena1, Linsey E Haswell2, Michael McEwan2
1RAI Services Company, Winston-Salem, NC, United States.
Frontiers in toxicology
|July 15, 2025
概括
这项研究提出了动脉样硬化斑块进展的不良结果途径 (AOP),使用香烟烟雾引起的氧化应激作为起点. 该框架为评估心血管疾病风险提供了动物试验的替代方案.
科学领域:
- 毒理学和药理学 毒理学和药理学
- 心血管疾病研究研究
- 监管科学 监管科学
背景情况:
- 负面结果途径 (AOP) 是风险评估中使用的机制框架.
- 动脉样硬化进展的评估通常依赖于动物模型,这些模型耗时且在道德上复杂.
- 需要使用替代方法来评估暴露对动脉样硬化的健康影响.
研究的目的:
- 制定和提出一种用于动脉样硬化斑块进展的AOP.
- 建立香烟烟雾暴露和心血管疾病之间的机械联系.
- 为监管评估动脉样硬化风险提供一个框架,减少对动物研究的依赖.
主要方法:
- 遵循经济合作与发展组织 (OECD) 关于AOP开发的指导方针.
- 收集了证据,将香烟烟雾引起的氧化应激与分子发起事件 (MIE) 联系起来.
- 确定了MIE下游的关键事件 (KE),包括炎症和内皮功能障碍.
主要成果:
- 提出了一个AOP,详细说明了从氧化应激 (MIE) 到动脉样硬化斑块进展的序列.
- 突出重点事件,如对促炎媒介的升高调节,氧化耗尽和内皮功能障碍.
- 确定这些KE的变化有助于心血管疾病发病率和死亡率.
结论:
- 开发的AOP提供了评估动脉样硬化进展风险的机制叙述.
- 该AOP框架支持使用体外和临床数据,减少对体外动物研究的需求.
- 拟议的途径为临床前测试和动脉样硬化的监管风险评估提供了一个强大的替代方案.
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