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在小鼠暴露于GCR后,cGAS/STING通路调解了加速肠道细胞衰老和SASP

Santosh Kumar¹, Kamendra Kumar¹, Jerry Angdisen¹

¹Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Research Building, Room E504, 3970 Reservoir Rd., NW, Washington, DC 20057, USA.

|November 26, 2025

概括

银河系宇宙辐射 (GCR) 模拟导致老鼠肠道中持久的DNA损伤,氧化应激和免疫激活. 这种太空辐射暴露导致肠道功能障碍和屏障损害,需要为宇航员采取保护性对策.

科学领域:

太空医学和辐射生物学
胃肠道 (GI) 健康和辐射伤害
辐射诱导的组织损伤的分子机制

背景情况:

长期的太空任务使宇航员暴露在银河系宇宙辐射 (GCR) 中,这对健康构成重大风险.
由高电荷,高能量 (HZE) 离子组成的GCR可以导致慢性组织损伤.
了解GCR对胃肠道的影响对于宇航员健康至关重要.

研究的目的:

为了研究模拟GCR暴露后小鼠的肠道结果.
在低剂量GCR模拟 (GCRsim) 后识别肠道中的分子和功能变化.
评估GCRsim对肠道完整性和功能的长期影响.

主要方法:

野生类型的小鼠接受了33离子混合场GCR模拟 (GCRsim) 的低剂量 (50cGy).
在暴露5个月后,分析了肠道组织和血清,以检测DNA损伤,氧化应激,衰老和免疫标记.
对营养载体,肠道激素和DNA降解核酶进行基因表达分析;还测量了肠道损伤的生物化学标志物.

主要成果:

GCRsim诱导了持续的DNA双链断裂 (DSB),氧化应激和肠上皮细胞 (IEC) 衰老.
观察到循环中的LINE-1DNA升高和DNA清除受损,以及cGAS-STING先天免疫通路的慢性激活.
GCRsim改变了营养吸收基因表达,破坏了肠道屏障 (通过降低血清素和增加I-FABP表示),并影响了肠道激素水平.

结论:

低剂量GCR模拟会导致持续的肠道功能障碍,包括DNA损伤,衰老和免疫失调.
细胞外DNA清除受损和慢性cGAS-STING通路激活有助于GCR诱导的胃肠道损伤.
这些发现强调了在深空任务期间需要采取对策来保护宇航员的胃肠道健康.

关键词:

造成的DNA损伤是DNA损伤.cGAS/STING信号传输系统提供信号.银河系宇宙辐射的宇宙辐射.这是一种炎症炎症炎症炎症.肠道屏障的完整性肠道屏障的完整性衰老是一种老化.与衰老相关的分泌表型表型

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