在多克索鲁比辛,环胺和帕克利塔克塞尔化疗治疗后,肠道,微生物组和认知的变化
Bailey Cronin1,2, Sangam Kandel3, Taylor McElroy1,2,4
1Division of Radiation Health, University of Arkansas for Medical Sciences, Little Rock, AR, US.
Scientific reports
|January 10, 2026
概括
乳腺癌的化疗可以导致认知障碍 ("化学大脑") 和焦虑在幸存者. 这项对小鼠的研究揭示了化疗诱导的肠道失调和神经炎症,影响了社会记忆和行为.
科学领域:
- 神经科学是一个神经科学.
- 在瘤学瘤学.
- 微生物组研究 微生物组研究
背景情况:
- 乳腺癌是美国女性最常诊断的癌症,由于有效的治疗方法,其存活率很高.
- 化疗诱导的认知障碍 (CICI),或"化脑",影响超过78%的乳腺癌幸存者.
- 了解长期治疗对幸存者生活质量的副作用至关重要.
研究的目的:
- 研究组合化疗 (AC-T) 对认知功能和行为的长期影响.
- 探索与AC-T治疗相关的潜在的多原子机制,包括神经炎症和肠道微生物组变化.
主要方法:
- 使用了一种转化小鼠模型,该小鼠接受了多克索鲁比 (DOX),环胺 (CYP) 和帕克利塔克塞尔 (PTX) 的腹腔内注射.
- 在治疗后30天使用社会记忆和焦虑测试评估认知和焦虑类行为.
- 进行RNA测序,西部斑分析和蛋白质组学以分析神经和肠道组织中的分子变化.
主要成果:
- 接受AC-T治疗的小鼠在社交记忆中表现出缺陷,增加了类似焦虑的行为.
- 分子分析揭示了与神经发生,轴突引导,神经传递和直接早期基因 (IEG) 相关的下调转录.
- 蛋白质组学在AC-T治疗小鼠的肠道组织中发现了炎症标记的增加,以及形态变化和肠道失生症.
结论:
- 组合化疗 (AC-T) 在小鼠模型中诱导认知缺陷和焦虑类行为.
- 化疗治疗对神经发生,神经传递和IEG表达有负面影响.
- AC-T治疗导致肠道炎症,失生症和形态变化,这表明肠-大脑轴参与化疗副作用.
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