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自由血红素加剧了抗癌疗法诱导的结肠损伤
Philippa Seika1, Monika Janikova1,2, Sahana Asokan1,3,4
1Department of Surgery, Division of Surgical Sciences, Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Frontiers in immunology
|June 21, 2023
概括
结肠中的自由血红素积累会放大DNA损伤和炎症,在癌症治疗后导致胃肠综合征 (GIS). 血红氧酶-1 (HO-1) 和血素 (Hx) 在这个过程中起着关键作用.
科学领域:
- 胃肠病学 胃肠病学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 癌症放射治疗和化疗可以通过不清楚的机制引起胃肠道炎症和出血.
- 血积累及其相关蛋白质,血氧酶-1 (HO-1) 和血素 (Hx),与这些副作用有关.
研究的目的:
- 研究自由血红素及其相关蛋白质 (HO-1,Hx) 在化疗和放射治疗引起的胃肠道损伤中的作用.
- 阐明血红素影响结肠上皮细胞和巨细胞反应的机制.
主要方法:
- 从癌症患者接受放射或化学辐射治疗的结肠活检的分析.
- 采用了骨髓细胞特异性HO-1淘汰 (LysM-Cre:Hmox1) 和血素淘汰 (Hx) 的小鼠模型.
- 服用基 (PHZ) 诱导血液溶解并评估结肠损伤,DNA损伤和细胞增殖.
主要成果:
- 在治疗后患有胃肠道出血的患者中观察到HO-1+巨细胞和血素水平的增加.
- 骨髓细胞中的HO-1缺乏会加剧DNA损伤和血解反应中的增殖.
- 缺乏Hx导致血液溶解,DNA损伤和结肠炎症的增加,部分受到重组Hx的缓解.
结论:
- 结肠中的血积累有助于DNA损伤,异常的上皮细胞增殖和炎症,可能导致胃肠综合征 (GIS).
- HO-1和Hx在调节血红素毒性和保护结肠表皮方面发挥着至关重要的作用.
- 向血积累或调节HO-1/Hx通路可能提供治疗策略,用于管理与治疗相关的胃肠毒性.
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